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Objective: The aim of our study was to observe the efficiency and toxicity of oxaliplatin (L-OHP) combined with CF/5-FU in patients with advanced primary hepatocellular carcinoma.Methods: Twenty patients with advanced primary hepatocellular carcinoma had recurrence/metastasis after multiple courses of TACE (cisplatin and epirubicin, etc.).All patients were treated with FOLFOX4 regimen of the combination of oxaliplatin and leucovorin and 5-fluorouracil.Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred.The efficiency was evaluated according to RECIST criteria, and toxicities according to American National Cancer Institute Common Toxicity Criteria (NCI CTC), respectively.Results: Twenty patients were assessable for the objective efficiency and for toxicity.No patient achieved complete response (CR), 4 patients were partial response (PR), 8 patients were stable disease (SD), 8 patients were disease progression (PD); Time to tumor progression (TTP) of the patients ranged from 1.5 to 4.8 months, median TTP was 2.2 months; Overall survival (OS) of the patients ranged from 3 to 10.2 months, median OS was 5 months.The 2 patients serum AFP level decreasing.Sixteen patients relieved the symptoms obviously, stabilized or raised up Karnofsky Score.The toxicities (40%).Conclusion: FOLFOX4 regimen is effective and safe for patients with advanced primary hepatocellular carcinoma.It can be worthy of further clinical investigation.