Objective：The study aims to determine the risk factors affecting postoperative survival in patients with alpha-fetoprotein （AFP）negative（AFP＜20 ng/mL）hepatocellular carcinoma（HCC）. Methods：A total of 479 patients with HCC who underwent radical resection were recruited in the current study. Independent prognostic factors for AFP-negative HCC patients were determined using univariate and multifactorial Cox regression analysis. The Kaplan-Meier method was used to assess the probability of survival，and log- rank tests were performed. Results：Age（HR=1.047，95% CI：1.002-1.094），carcinoembryonic antigen（HR=1.151，95% CI：1.027- 1.290），carbohydrate antigen 19-9（HR=1.053，95% CI：1.002-1.105），aspartate aminotransferase（HR=1.031，95% CI：1.001-1.070） and tumor size（HR=1.289，95% CI：1.161- 1.432）were independent risk factors for survival in AFP-negative HCC patients. The elevated values of the 5 risk factors had negative impacts on prognosis and were independent risk factors for overall survival（OS）（P＜ 0.05）. OS was longer in AFP-negative HCC patients than in AFP-positive HCC patients（P＜ 0.001）. Conclusion：AFP-negative patients undergoing surgical treatment for HCC are required attention to liver function and tumor markers，especially in patients older than 65 years and with tumor size larger than 6 cm.