Objective To investigate the role and the underlying mechanism of the expression of DNA damage repair protein XPF in cisplatin resistance of renal cancer cells. Methods XPF level in different renal cancer cell lines ACHN

786-0 and Caki-1 was detected by Western blotting. After acquiring shXPF cells with XPF expression stably inhibited to a low level by shRNA technique

cisplatin resistance was detected in the shXPF cells and shNC cells (negative control) by colony formation assay and Annexin V-FITC/PI staining. β-galactosidase staining was used to detect cell senescence of shXPF cells. Results Among 786-0 cells

ACHN cells and Caki-1 cells

XPF was strongly expressed in ACHN cells

which showed highest resistance to cisplatin. After interfered by shRNA technique

ACHN-shXPF cells were acquired stably expressing lower level XPF

showing lower colony formation rate (P0.05) and higher percentage of apoptosis after cisplatin treatment. Additionally

the percentage of senescent cells was significantly higher in ACHN-shXPF than ACHN-shNC cells (P0.01). Conclusion The insensitivity of renal cancer cells to cisplatin might be related with the high expression of DNA damage repair protein XPF. Interfering the XPF expression in ACHN cells can promote cisplatin-induced apoptosis and cell aging

thus leading to higher sensitivity to cisplatin.