A low platelet count is one of the most sensitive tests for cirrhosis detection in patients with hepatitis C virus (HCV) infection. We evaluated whether the human platelet antigen (HPA) genotype could predict platelet count in HCV-positive patients.We genotyped the HPA 1, 2, 3, 5 and 15 polymorphisms in consecutive patients with HCV infection.Out of the 56 patients enrolled, 56.1% had liver cirrhosis. The mean platelet count was significantly lower in those with HPA1aa genotype than in those with HPA1ab/bb genotype. Platelet count did not differ among the other HPA polymorphisms. However, at logistic regression analysis, only the HPA3aa genotype and liver cirrhosis were independent predictors of a low platelet count.HPA3aa is an independent factor for a low platelet count in this cohort of patients with HCV chronic infection regardless of disease stage.