In the present study, we firstly provide evidence that co-cultured SMMC-7721-derived LCSLCs with LX-2 cells induced stemness of SMMC-7721 cells, including the increased sphere formation capability and expression of CD133 and CD44; meanwhile, upregulated expression of fibroblast activation protein α (FAP-α) in LX-2 cells.IL-6 and HGF may be the key communication molecules for the interaction between LCSLCs and HSCs, and that BrMC and chrysin could block these effects, thereby suppress co-culture-induced stemness of HCC. This evidence concerns the gene PROM1 and hepatocellular carcinoma.