Abstract: Objective To explore the therapeutic effect and safety of sorafenib combined with GEMOX regimen in the treatment of advanced hepatocellular carcinoma （HCC）. Methods In a retrospective analysis， 53 HCC patients in our hospital from March 2009 to April 2013 were assigned to receive sorafenib alone （Group A， n=26） or in combination with GEMOX regimen （Group B， n=27）. The curative effect was analyzed according to Response Evaluation Criteria in Solid Tumors （RECIST） version 1.1. The National Cancer Institute Common Toxicity Criteria （NCI-CTC） version 3.0 was employed to evaluate the adverse reaction. Survival analysis was performed using KaplanMeier method. Results All the 53 patients were evaluable for evaluation. There were no CR cases in both groups. In Group A， there were 2 cases of PR， 7 cases of SD and 17 cases of PD with the response rate （RR） and disease control rate （DCR） of 7.7％ and 34.6％. In Group B， there were 4 cases of PR， 9 cases of SD and 14 cases of PD with RR and DCR of 14.8％ and 48.1％. No significant differences were observed between 2 groups （P＞0.05）. The median progression free survival （PFS） and overall survival （OS） were 4.5 months and 8.4 months in group B， higher than 6.7 and 13.8 months in Group A with statistically significant difference （P＜0.05）. The main adverse reactions were hand foot syndrome， hypertension and diarrhea in Group A without bone marrow suppression. The most common adverse reactions in group B were bone marrow suppression， manifested as grade 1-2 leukopenia and thrombocytopenia. There were higher incidences of leucopenia， thrombocytopenia and hemoglobin decrease in Group B versus Group A. The major non hematologic toxicity of 2 groups was nausea and vomiting and liver damage. The renal damage， skin rash and peripheral neuritis were rare. Conclusion Sorafenib combined with GEMOX regimen is safe and effective for treatment of advanced HCC and most patients are tolerable. It can bring survival benefit to patients with advanced HCC.