Kanglaite, a type of Chinese medicine preparation, is considered a promising complementary therapy option for advanced hepatocellular carcinoma (HCC). Although an analysis of the published literature has been performed, the exact effects and safety are yet to be systematically investigated. Therefore, we conducted a wide-ranging online search of electronic databases to provide systematic conclusions; data from 31 trials with 2315 HCC patients were included. The results indicated that compared with conventional treatment (CT) alone, the combination of kanglaite with CT markedly prolonged patients’ 6-month overall survival (OS, P=0.003), 12-month OS (P<0.0001), 18-month OS (P=0.003), 24-month OS (P=0.03) and 36-month OS (P=0.0006) and significantly improved the overall response rate (odds ratio (OR) = 2.57, 95% confidence interval (CI) = 2.10–3.16, P<0.00001) and disease control rate (OR = 3.10, 95% CI = 2.42–3.97, P<0.00001) of patients. The quality of life (QoL), clinical symptoms and immune function of patients were also obviously improved after combined treatment. The incidence rates of nausea and vomiting (P=0.04), hepatotoxicity (P=0.0002), leukopenia (P<0.00001), thrombocytopenia (P<0.0001), gastrointestinal side effects (P=0.01) and fever (P<0.0009) were lower in the group receiving CT and kanglaite than in the group receiving CT alone. In summary, the combination of kanglaite and CT is safe and more effective in treating HCC than is CT alone, and its application in the clinic is worth promoting.