Our results showed clearly that PS341 could significantly suppress the proliferation, migration, EMT and the expression of stemness-related gene of HCC and CRC cells both in vitro and in vivo with the upregulation of FOXO3 and downregulation of CTNNB1, which shed some light on the future HCC and CRC treatment based on PS341. The gene discussed is CTNNB1; the disease is hepatocellular carcinoma.