Recent studies showed that pseudogenes can regulate the expression of their coding gene partners by competing for miRNAs. The E2F family plays a crucial role in the control of cell cycle checkpoint. E2F3P1 is a pseudogene of E2F3. Few studies focused on genetic variations on pseudogenes. In this study, we performed a case-control study to assess the association between single nucleotide polymorphisms (SNPs) in E2F3P1 and hepatocellular carcinoma (HCC) risk in 1050 hepatitis B virus (HBV)-positive HCC cases and 1050 chronic HBV carriers. Logistic regression analysis was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and HCC risk. We found that the variant CT/TT genotypes of rs1838149 were associated with a significantly decreased risk of HCC (adjusted OR=0.66, 95% CIs=0.51-0.86, P=0.002) compared to those with wildtype CC homozygote. Furthermore, the AA genotype of rs9909601 had an increased HCC risk with an adjusted OR of 1.41 (95% CIs=1.07-1.86), and the A allele of rs9909601 was significantly associated with HCC risk compared to those with the G allele (adjusted OR=1.17, 95% CIs=1.03-1.33, P=0.017). These results indicate that genetic variations in the pseudogene E2F3P1 may confer HCC risk. Recent studies showed that pseudogenes can regulate the expression of their coding gene partners by competing for miRNAs. The E2F family plays a crucial role in the control of cell cycle checkpoint. In this study, we performed a case-control study assess assess the association between single nucleotide polymorphisms (SNPs) in E2F3P1 and hepatocellular carcinoma (HCC) risk in 1050 hepatitis B virus (HBV) -positive HCC cases and 1050 chronic HBV carriers. Logistic regression analysis was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and HCC risk. We found that the variant CT / TT genotypes of rs1838149 were associated with a decreased decreased risk of HCC OR = 0.66, 95% CIs = 0.51-0.86, P = 0.002) compared to those with wildtype CC homozygote. Furthermore, the AA genotype of rs9909601 had an increased HCC risk with an adjusted OR of 1.41 (95% CIs = 1.07-1.86), and the A allele of rs9909601 was significantly associated with those with the G allele (adjusted OR = 1.17, 95% CIs = 1.03-1.33, P = 0.017) results indicate that genetic variations in the pseudogene E2F3P1 may confer HCC risk.