The efficacy of adjuvant interferon treatment for the management of patients with viral hepatitis-related hepatocellular carcinoma (HCC) following curative treatment is controversial. We have conducted a systematic review with meta-analysis to assess the effects of adjuvant interferon therapy on survival outcomes. Randomized and nonrandomized studies (NRSs) comparing adjuvant interferon treatment with the standard of care for viral hepatitis-related HCC after curative treatment were included. CENTRAL, Medline, EMBASE and the Science Citation Index were searched with complementary manual searches. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS). Nine randomized trials and 13 NRSs were included in the meta-analysis. These nine randomized trials included 942 participants, of whom, 490 were randomized to the adjuvant interferon treatment group and 452 to the control group. The results of meta-analysis showed unexplained heterogeneity for both RFS and OS. The 13 NRSs included 2214 participants, of whom, 493 were assigned to the adjuvant interferon treatment group and 1721 to the control group. The results of meta-analysis showed that, compared with controls, adjuvant interferon treatment significantly improved the RFS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.52-0.84, I(2) = 29%] and OS (HR 0.43, 95% CI 0.34-0.56, I(2) = 0%) of patients with hepatitis C virus-related HCC following curative treatment. There was little evidence for beneficial effects on patients with hepatitis B virus-related HCC. Future research should be aimed at clarifying whether the effects of adjuvant interferon therapy are more prominent in hepatitis C patients with sustained virological responses.