The recurrence rate of hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR) is very high. Many clinical trials have explored the efficacy of several treatment modalities to prevent recurrence, including adjuvant and chemopreventive therapy, but they have often reported contradictory findings. As a result, most liver guidelines and liver seminars do not unequivocally endorse adjuvant or chemopreventive therapy for HCC patients after potentially curative HR. To examine the available evidence on this question, we comprehensively searched PubMed for controlled studies that included a supportive care or placebo control arm, and we used the GRADE system to classify and assess the results.