Fas/FasL polymorphisms, which are related to apoptosis, might influence the clearance of hepatitis B virus (HBV) infection and the occurrence of hepatocellular carcinoma (HCC). This study was performed to determine whether Fas and FasL promoter polymorphisms are associated with clinical outcome in chronic HBV infection.A total of 1,095 Korean subjects were prospectively allocated to two different groups: 'the chronic carrier group' (CC; n = 666), who were repeatedly hepatitis B surface antigen (HBsAg)-positive, and 'the spontaneous recovery group' (SR; n = 429), who were HBsAg-negative with antibodies to HBsAg and hepatitis B core antigen. In addition, the CC group was subcategorized into chronic hepatitis and HCC subgroups. Fas promoter polymorphisms at -1377G>A and -670A>G and the FasL promoter polymorphism at -844C>T were analyzed for and the genotype distributions of subjects were compared.There were no significant associations between Fas or FasL promoter polymorphism with the HBV clearance and HBeAg clearance. However, -1377G>A in Fas promoter region showed protective effect to HCC occurrence (RH = 0.70, p = 0.03).Fas-1377G>A polymorphisms might be involved in the pathogenesis of human HCC.