Background: EASL guidelines for management of HCC recommends assessing tumor response according to mRECIST at all stages of the disease (EASL guidelines, J Hep 2018). Several studies have reported that objective response by mRECIST predicted overall survival (OS) but definitive data are still lacking. Methods: The PubMed database and ASCO meeting library were searched for full reports of randomized trials in patients with advanced HCC treated by systemic therapy up to August 31, 2018. We search strategy used the following terms: HCC, mRECIST, OS and objective response rate (ORR). We assess the association between ORR and OS in a meta-analysis of pooled data by using random effects model comparing patients achieving objective response (complete or partial response) versus non responders (stable disease, progressive disease) and displayed the results as per hazard ratio (HR, 95% CI). Results: Among 14 articles assessing response by mRECIST to systemic therapies in randomized studies in advanced HCC, 4 studies (5 trials) including 1,463 patients were considered eligible. Systemic therapies tested included lenvatinib, sorafenib, brivanib and nintedanib. Overall, ORR as per mRECIST ranged from 11.5% to 18.8%, being the median OS for responders of 18.5 to 27.2 mo (as opposed 8.9 to 11.4 for non-responders). As per random effects model, the HR for overall survival (responders versus non responders) was 0.47 (95% confidence interval 0.34–0.66, p<0.001). Conclusions: Objective response by mRECIST to systemic therapies in patients with advanced HCC is significantly and strongly associated to OS. Patients achieving an objective response can expect a significantly longer OS.