The most silenced TSGs, including HHIP, MT1M, PZP, and TTC36 were consistently reactivated by SpdCas9-VPR and MS2-MCP-p65-HSF1 epigenetic editing tools in both HCC cell lines tested in a hit-and-run (transient transfection) approach. This evidence concerns the gene HSF1 and hepatocellular carcinoma.