ObjectiveTo systematically evaluate the difference in recurrence-free survival rate, hepatocellular carcinoma (HCC) recurrence rate, all-cause mortality rate, and liver-related mortality rate between hepatitis C-related HCC patients receiving oral direct-acting antiviral (DAA) and those receiving non-DAA (NDAA) treatment regimen. MethodsCNKI, Wanfang Data, VIP, CBM, PubMed, Embase, and Cochrane Library were searched for Cohort studies of DAA in the treatment of hepatitis C-related HCC patients published before December 2020, and quality assessment and meta-analysis were performed. ResultsA total of 10 cohort studies were included in this study, with 3108 patients in total. The meta-analysis showed that compared with NDAA regimen, DAA treatment significantly increased recurrence-free survival rate (risk ratio ［RR］=1.38, 95% confidence interval ［CI］: 1.10-1.72, P=0.005) and significantly reduced HCC recurrence rate (RR=0.52, 95%CI: 0.42-0.63, P＜0.000 01), all-cause mortality rate (RR=0.42, 95%CI: 0.32-0.55, P＜0.000 01), and liver-related mortality rate (RR=0.37, 95%CI: 0.18-0.76, P=0.007) in hepatitis C-related HCC patients. ConclusionDAA treatment is beneficial and safe for hepatitis C-related HCC patients.