Here, we demonstrated that the cell-cycle regulator and senescence-associated gene CDKN1A (p21WAF1/CIP1) was significantly induced in HNF4α-overexpressed prostate cancer cells, rather than CDKN1B (p27) and p53 (Supplementary Figs. S7a and S8a), indicating that HNF4α-meditated senescence in prostate cancer cells could be operated in a p53-independent manner, as evidenced by its promotion of cellular senescence in prostate cancer cells with different p53 background. Here, HNF4A is linked to Familial prostate cancer.