In line with previous findings, here we confirm the relationship between miR-122/SerpinB3 axis and stemness markers in HCC specimens, as well as the opposite modulation of stem cell features exerted by miR-122 and SerpinB3 in HCC cell lines, suggesting the targeting of SerpinB3 as a possible mechanism contributing to miR-122 active role in reducing HCC stemness. This evidence concerns the gene SERPINB3 and hepatocellular carcinoma.