AimsTo compare the safety and efficacy of TACE using raltitrexed, oxaliplatin and epirubicin with 5-fluorouracil, oxaliplatin and epirubicin for patients with unresectable hepatocelluar carcinoma.ResultsMedian overall survival (OS) was 7.4 months in the raltitrexed group [95% confidence interval (CI): 5.4, 9.4) and 5.8 months in the control group (95% CI: 5.2, 6.4; P = 0.177). The median progression-free survival (PFS) time was significantly higher in the raltitrexed group (3.6 months, 95% CI: 2.8, 4.4) than in the control group (2.6 months, 95% CI: 2.2, 3.0; P = 0.038). The disease control rate (DCR) was higher in the raltitrexed group than in the control group (40% versus 30.4%; P = 0.353). The incidence of adverse events was similar between the two groups.Materials and MethodsFrom January 2012 to December 2014, 86 patients with unresectable HCC were treated with TACE using the combination of raltitrexed, oxaliplatin and epirubicin (raltitrexed group), and the combination of 5-fluorouracil, oxaliplatin and epirubicin (control group). The primary endpoint was OS, and the secondary endpoints were PFS, DCR and adverse events.ConclusionsAlthough the study did not meet its primary endpoint, raltitrexed group reach a higher PFS, which suggests that this combination regimen of TACE as alternative may confer some benefits to selected patients.