The present study was conducted for the comparative evaluation of Polychlorinated Biphenyls (PCBs) and Organochlorine Pesticides (OCPs) in the serum samples of diagnosed cancer patients and healthy humans of Karachi. Impact of these chemicals on the serum cell free DNA (cf-DNA), Cholesterol, Alkaline Phosphatase and Total Protein contents was also ascertained in the studied cohort. This was a preliminary work on the role of PCBs and OCPs in the etiology of cancer in Pakistan. A random collection of fasting blood samples from diagnosed cancer patients having various malignancies and healthy humans was carried out with informed consent of the donors at various hospitals and health care centers of Karachi. Serum was separated within 2 hours of collection and was used for subsequent analysis. Analysis of PCBs and OCPs was carried out on Gas Chromatograph coupled with Electron Capture Detector. Serum cf-DNA was analyzed on NanoDrop Spectrophotometer while serum Cholesterol, ALP and Total Protein contents were analyzed on Roche/Hitachi diagnostic analyzers. Levels of the seven tested PCBs (PCB 28, PCB 52, PCB 101, PCB 138, PCB 153, PCB 180 and PCB 209) were significantly higher in the cancer group compared with the control group. PCBs were detected in 93.98 % of the cancer cases and 93.75 % of the normal subjects. Mean level of ΣPCBs was found significantly elevated in the cancer group (2.711 mg/kg) compared with the control group (0.536 mg/kg). PCB 52 was the most prevalent chemical with a mean level of 2.044 mg/kg in the cancer group and 0.134 mg/kg in the control group. It was observed that concentrations of PCBs increased linearly with the increasing age of the cancer patients. On the other hand, OCPs were detected in 97.59 % of the cancer cases and 93.75 % of the normal subjects. Mean concentration of total OCPs was found elevated in the cancer group (0.611 mg/kg) compared with the control group (0.321mg/kg). Endosulfan was the highest prevalent OCP with mean concentration of 0.214 mg/kg in the cancer group and 0.170 mg/kg in the control group. DDT metabolite - 4,4-DDE was found significantly elevated in the cancer group with a mean level of 0.131 mg/kg compared to the control group (0.020 mg/kg). Highest mean concentration of ΣPCBs was found in cases of the female genital system while highest mean of ΣOCPs was detected in the breast cancer cases. Significantly elevated level of cf-DNA was detected in the cancer group with a mean value of 5584.2 ng/μl compared with control group (1758.8 ng/μl). Detection of cf-DNA was 56.45 % in the cancer group and 36.84 % in the control group. Mean cholesterol level was found significantly diminished in the cancer group (116±22 mg/dl) compared with the control group (158.7±33 mg/dl). ALP activity was found elevated in the cancer cases with a mean level of 125±48 U/L compared with the normal counterparts (109±28 U/L). Mean total protein contents were found reduced in the cancer cases (6.2±0.58 g/dl) compared to normal subjects (7.2±1 g/dl). Cases having higher residues of PCBs and to some extent of OCPs has shown elevated concentrations of cf-DNA, comparatively higher levels of cholesterol and ALP and reduced total protein contents. In light of the obtained results, it has concluded that PCBs and OCPs are positively associated with the etiology of cancer. Moreover, PCBs and OCPs adversely affect other biological parameters of the body which may ultimately result into various cancers in humans.