In this study it was reported that toxic elements including cadmium (Cd), arsenic (As) and nickel (Ni) in the drinking water is associated with increased incidences of cancers. There is a compelling evidence in support of negative associations between essential traces and toxic elements in different types of cancer. The antagonistic effects between essential elements such as selenium (Se), zinc (Zn) and toxic elements; arsenic, cadmium and nickel status are linked with the imbalances of essential traces and toxic elements in body fluid and human tissues. Epidemiologic studies suggests that the deficiency of essential trace elements and exposure to the toxic elements might be linked with increased risk of cancer. In this study different methodologies were adopted to analyze trace quantity of essential and toxic element in human biological along with water and food samples. The preparation of different samples and their pretreatment were optimized in order to maximize the recoveries, precision and accuracy for under study analytes, using certified reference material of matched matrices. In present study patient suffering from different types of cancers (like: mouth, lung, bladed, liver, skin and gynecological) in both genders (males and females) were collected from cancer hospitals located in different regions of Sindh Pakistan. The biological samples (blood and scalp hair) along with biochemical parameters were collected. For comparative purposes, the biological samples from referents (males and females) have same age group (ranged 35–65 years) as a referents were also analyzed. Both referents and patients have the same socioeconomic status, localities and dietary habits. The biological samples (blood and scalp hairs) of male biopsy proved subjects having bladder, lung and liver cancer and non-cancerous subjects belonging to arsenic (As)-exposed area of southern parts of Pakistan were analysed for As contents. The As levels in drinking water of understudy area were 3–15-fold higher than the permissible level (<10 mg/L). It was observed that the lung cancer patients have 20–35% higher levels of As in both biological samples as compared to bladder cancer patients, might be due to smoking habit. This study proven the positive associations between arseniccontaminated water, food and cigarette with different types of cancers. The mouth cancer incidences are increased among peoples, who have habits of chewing tobacco with gradients (areca nut and betel quid) and smoking in Pakistan. To measure the concentration of Cd and Zn in mouth cancer patients (MCPs) of both genders. It was observed that the levels of Zn were lower, whereas Cd was higher in the blood and scalp hair samples of MCPs as compared to referent subjects (p < 0.001). The referents chewing and smoking tobacco have high level of Cd in both biological samples as compared to those which do not have habit of smoking or chewing tobacco (p < 0.012). The Cd/Zn ratio was higher in MCPs than referent subjects. The As and Se in acid digests of biological samples of As exposed group comprises, female have skin lesions (ESL), skin cancer (ESC), admitted in cancer hospitals, and exposed referents not having both diseases (ER), belongs to As exposed area of Pakistan. The both elements in acid digested biological sample were preconcentrated by complexing with chelating agent (ammonium pyrrolidinedithiocarbamate), and resulted complexes were extracted into non-ionic extractant (Triton X- 114), prior to analysis by electrothermal atomic absorption spectrometry. The enhancement factor of about 25 was obtained by pre-concentrating 10 mL of sample solutions. The accuracy of the optimized procedure was evaluated by using certified reference material (BCR 397). The biological samples of ESC patients had 2–3 folds higher As and lower Se levels as compared to referent patients (p<0.001). The higher concentration of As and lower Se levels in biological samples of cancerous patients are consisted with reported studies. The relationship between carcinogenic elements, arsenic, cadmium, and nickel, and anti-carcinogenic elements, selenium and zinc, in the scalp hair and blood of different female cancer patients (breast, cervix, mouth and ovarian) whereas for male cancer patients (urinary bladder, lung, mouth and esophagus), both scalp hair and blood samples were analysed. The referents of both genders were also selected. The male patients and referents were all smokers. The mean concentrations of As, Cd, and Ni were found to be significantly higher in the scalp hair and blood samples of cancerous patients as compared to referents, while inverse results were obtained in case of essential elements Zn and Se (p < 0.01). The study revealed that the carcinogenic processes are significantly affecting the trace elements burden and mutual interaction of essential trace and toxic elements in the cancerous patients.