The aim of this study was to compare the clinical effect of tacrolimus (TAC) versus cyclosporine (CycA) in post-transplant hepatic cancer patients undergoing adriamycin hydrochloride (ADM) chemotherapy. Patients with advanced hepatic cancer who underwent liver transplant and subsequent therapy between March 2007 and March 2009 in our hospital were selected for this study. All of these patients were treated with chemotherapeutic agent adriamycin, with respect to immunosuppressant, whereas they received either TAC or CycA, and hence represented two groups, TAC and controls, respectively. The short- and long-term outcomes of two therapies, ADM + TAC and ADM + CsA, were compared. The TAC group patients showed improved remission compared to the control group (40 cases with 46.0 % versus 32 cases with 31.1 % remission, respectively). The 5-year survival in TAC group was significantly prolonged (20.7 %) compared to that of the controls (8.7 %). The short-term outcomes, such as serum levels of calcium, biomarkers of cardiac toxicity/functioning, and regulatory T lymphocytes counts (markers of immune functioning), were found to be significantly more auspicious with TAC treatment than with CycA. Our study showed that use of TAC plus ADM resulted in improved patient survival, tolerance of the graft, and remission compared to CycA combined with ADM. The serum levels of various markers in the short follow-up analysis indicated a better cardiac and immune functioning with TAC than with CycA treatment.