Our study found that over-expression of let-7c inhibited the activation of CDK6, pRb and E2F2 and that, conversely, inhibition of let-7c enhanced the expression of these proteins, indicating that let-7c suppressed the expression of CDC25A protein and subsequently led to the down-regulation of CDK6, CyclinD1, pRb and E2F2 proteins in human HCC. This evidence concerns the gene CDK6 and hepatocellular carcinoma.