Hepatocellular carcinoma (HCC) is a global health problem and ranks sixth among malignant tumors. It is associated with significant morbidity and is 2nd leading cause of cancer associated deaths. HCC is a preventable cancer because its development is associated with known risk factors. Hepatitis B and C virus infection are among the main risk factors. In Pakistan 10 million individual are infected by HCV. Chronic HCV infection leads to liver fibrosis and cirrhosis. HCV –associated cirrhosis is major risk factor for HCC. About 70-80% of HCV infected individual develop develop chronic hepatitis and not all cirrhotic develop HCC, suggesting that host factors also play important role in HCC development. Pathogen recognition receptors (PRRs) which include Toll like Receptors (TLRs) play an important part in host innate immune response. Inherited genetic polymorphism of TLR genes can affect their function and may alter susceptibility to disease and cancer. Chronic inflammation play critical role in HCC development. TLR2 which can sense viral proteins and induces strong inflammatory response resulting in chronic persistent hepatitis. Recent studies on TLR2 gene polymorphisms including the -196 to –174del/ins had reported their association with different malignancies including HCC. In this case control genetic association studyfrom 347subjects were randomly selected which included 150 controls, 100 HCV patients and 100 individual with HCV associated HCC. Genotypes and allelic frequencies of TLR2 polymorphism were determined by melting curve analysis by Real Time PCR were determined. Statistical analysis was performed and genotypes were also tested for deviation from Hardy-Weinberg proportions. The subjects of study population were from Faisalabad and adjacent districts who attended Allied Hospital Faisalabad. The genotyping of TLR2-196 to -174del/ins polymorphism was performed by Real Time PCR melt curve analysis. The results revealed that TLR-2 -196 to -174del polymorphism was significantly associated with risk of HCC in HCV infected subjects. The deletion allele frequency in HCV associated HCC was 33% as compared to 15.3% in controls. Higher frequency was also observed in cases with del/ins allele genotype polymorphism (45% in cases and 34.7% in controls). No risk association was observed in healthy subjects for HCV infection. Moreover del/del genotype was also associated with higher viral loads.