Objective To clarify the factors influencing long-term prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy, and to explore the value of preoperative plasma prealbumin (PA) in assessing the long-term prognosis. Methods We retrospectively analyzed the clinical and follow-up data of HCC patients who underwent hepatectomy in Eastern Hepatobiliary Surgery Hospital between Dec. 2011 and Mar. 2012. Univariate and multivariate Cox regression analyses were used to analyze the effects of preoperative factors on the overall survival time and recurrence of patients. According to the content of preoperative plasma PA, the patients were divided into high PA group (preoperative PA content was higher than 152 mg/L) and low PA group (preoperative PA content was lower than 152 mg/L); then the difference of prognosis between the two groups were compared by Kaplan-Meier methods. Results A total of 373 HCC patients undergoing hepatectomy were included in this study. The median survival time was 32.3 months and the median recurrence time was 20.5 months. Univariate and multivariate analysis showed that tumor size (P=0.003), TNM stage (P<0.001), preoperative PA content (P=0.034), and vascular invasion (P=0.027) were the independent risk factors for long-term overall survival time of patients after hepatectomy; while TNM stage (P<0.000 1), preoperative PA content (P=0.002), and vascular invasion (P=0.048) were the independent risk factors for recurrence of patients after hepatectomy. The median overall survival time and median recurrence time of patients in the high PA group were both significantly longer than those in the low PA group, respectively (median overall survival time: 41.3 months vs 31.7 months, P<0.000 1; median recurrence time: 28.8 months vs 14.4 months, P<0.000 1). Conclusion Low preoperative PA content is an independent risk factor for long-term overall survival and recurrence of HCC patients after hepatectomy.