Objective To study the preventive effects of vitamin K2 on tumor recurrence in patients with hepatocellalar carcinoma (HCC) after radical resection. Methods The clinical data of 50 patients with HCC who received radical resection from March 2006 to March 2007 in No. 181 Hospital of PLA were analyzed retrospec-tively. All the patients were divided into 2 groups according to the random number table. Twenty-six patients in vitamin K2 group were administered with menatetrenone (45 mg per day), and the rest 24 pateints were in the control group. The accumulative and tumor-free survival rates, differences between the 2 groups, multivariate factors for prognosis were analyzed by Kaplan-Meier curve, Log-rank test and Cox regression model, respectively. Results During a period of 36 month follow-up, 10 patients died and 28 had tunor recurrence. The 1-, 2-, 3-year accumulative survival rates were 96%, 92% and 83% in vitamin K2 group, and 96%, 82% and 63% in control group (χ2 = 3.61, P > 0.05). The 1-, 2-, 3-year tumor-free survival rates were 92%, 60% and 38% in vitamin K2 group, and 75%, 42% and 12% in control group, with significant difference between the 2 groups (χ2 =5.61, P <0.05). Univariate and multivariate Cox proportional hazard analysis showed that without taking menate-trenone, the preoperative level of alpha fetoprotein (AFP) ≥800 μg/L and vascular invasion were the indepen-dent risk factors for tumor recurrence. Conclusions Vitamin K2 has a suppressive effect on tumor recurrence of HCC, while patients with AFP≥800 μg/L before operation or with vascular invasion have poor prognosis.