Using univariate Cox regression analysis, RNF135 methylation (HR = 1.960; 95% confidence interval (CI): 1.367–2.810; P <0.001), tumor stage (HR = 2.375; 95% CI: 1.646–3.426; P <0.001) were associated with increased risk of HCC death. This evidence concerns the gene RNF135 and hepatocellular carcinoma.