OBJECTIVE: To investigate the effect of different doses of oxaliplatin on the efficacy and safety and related indexes of patients with hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). METHODS: 100 HCC patients were randomly divided into control group (50 cases) and observation group (50 cases). After TACE, control group received arterial infusion chemotherapy of 40 mg/m2 oxaliplatin, once a day+20 mg Epirubicin hydrochloride for injection, once a day, with little lipiodol. Observation group received arterial infusion chemotherapy of 80 mg/m2 oxaliplatin (the same usage with control group)+Epirubicin hydrochloride for injection (the same dosage with control group), with little lipiodol. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), white blood cell count (WBC) and alpha-fetoprotein (AFP) in 2 groups after 3 d treatment were observed, and the total overall survival (OS) and the incidence of adverse reactions were followed-up. RESULTS: Abdominal pain, incidences of nausea and vomiting, ALT, AST and TBIL in observation group were significantly higher than control group, WBC was significantly lower than control group, the differences were statistically significant (P<0.05). There were no significant differences in fever, hair loss, incidence of peripheral neurotoxicity, OS in 1 year and 3 years, and AFP in 2 groups (P>0.05). CONCLUSIONS: Compared with 40 mg/m2 oxaliplatin, 80 mg/m2 can reduce the incidence of abdominal pain, nausea, vomiting, but other effects are poor than 40 mg/m2, and it can not prolong the survival time of patients.