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Objective: The aim of the research was to study peptidylarginine deiminase type 4 (PAD4/PADI4) expression and its tumorigenic mechanism in hepatocellular carcinomas. Methods: Expressions of PADI4 and p53 were investigated in tumors and non-tumor tissues by Western blot in patients with hepatocellular carcinomas. We constructed plasmid of PADI4-Flag and transfected it in Hela cells to investigate the mechanism. Results: Western blot analysis showed higher PADI4 expression in hepatocellular carcinomas than in the surrounding healthy tissues. Furthermore, by Western blot, wedetected decreased p53 levels in the tumor tissues of patients with hepatocellular carcinomas compared to surrounding healthy tissues. In Hela cells transfected with PcDNA3.0-Flag-PADI4 plasmid, the expression of p53 decreased obviously.Conclusion: Our results suggest that PADI4 elevated in the tissues of hepatocellular carcinomas and induced tumorigenic by down-regulating p53 expression.