Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has an increasing incidence in Egypt. Hepatitis virus (HCV and HBV) are the major risk factors for developing HCC. IL-1β, a proinflammatory cytokine has been suggested to affect the hepatic carcinogenesis. Aim of the work: Was to evaluate the role of IL-1β polymorphism in the occurrence of HCC on top of viral versus none-viral etiology. Patients and Methods: The study included 178 patients with HCC (74 with HCV, 48 with HBV, and 56 without hepatitis virus) and 90 healthy volunteers represented the control group. The polymorphism in IL-1β –31 gene was investigated by polymerase chain reaction and restriction fragment length polymorphism. Quantitative determination of IL-1β serum level was performed using ELISA technique. Results: The frequency of TT genotype was higher in HCC patients with HCV when compared to HCC patients without viral hepatitis, and the control group (43.2%, 25% and 26.7%, respectively). We observed that the dominant model (TT and CT genotypes) were associated with increased HCC risk in HCV or HBV patients compared to the control group with odd ratio and 95%CI of 2.64 (1.3-5.3) and 2.77 (1.2-6.2) respectively. In addition, the T allele was more frequent in HCC patients with HCV or HBV when compared to none viral HCC and the control group (60.8%, 56.2%, 42.9 and 42.2%, respectively). Serum IL-1β level was elevated in all HCC groups as compared to the control group (p<0.05). Serum level of IL-1β was considerably increased in individuals with TT genotype or T allele as compared to other genotypes and allele (p<0.0001). Conclusion: IL-1β TT genotype and T allele which are associated with high blood IL-1β level may increase the risk of HCC in patients with chronic viral hepatitis.