Abstract： Objective To investigate the efficiency and safety of sirolimus-based and tow-dose steroid immunosuppression after liver transplantation for the patients with hepatocellular carcinoma (HCC). Methods Ninety-two patients with HCC beyond Milan criteria underwent liver transplantation from March 2004 to October 2006 in our center, and 89 patients were taken into study. The former 54 patients received tacrolimus-baesd immunosuppression, and the subsequent 35 patients were subjected to sirolimus-based immunosuppression. Both of them were followed up after operation. The following indexes including liver and kidney function, blood glucose and cholesterol, HCC recurrence rate, infection rate, acute rejection rate, one-year survival rate and drug side effect were tested. Results There was significant difference between the two groups in one-year HCC recurrence rate, 3-month infection rate, one-month high glucose rate, one-year high cholesterol rate and renal function damage rate. Conclusions Sirolimus-based and tow-dose steroid immunosuppression is safe and effective for the patients with HCC. The protocol not only suppressed rejection actively, but also cut down HCC recurrence rate notably, and decreased infection rate, high glucose and renal function damage rate, though it increased high cholesterol rate.