The aim of the present study was to explore the effect of silencing wild-type p53-induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase-3, caspase-3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl-2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated (p)-p38 MAPK. Reverse transcription-quantitative polymerase chain reaction was used to detect expression of p53, Bax, Bcl-2 and caspase-3 mRNAs. Compared with control, apoptosis of SKOV3 cell was significantly increased following Wip1 siRNA silencing. Wip1 silencing also resulted in a significant increase of p53 and p-p38 MAPK expression, as well as increased cleaved caspase-3/caspase-3 and Bax/Bcl-2 protein ratios. No significant differences were observed in apoptosis and apoptosis-related protein expression in the control siRNA transfected cells. The present study demonstrated that Wip1 silencing promotes apoptosis of human ovarian cancer SKOV3 cells by activation of the p38 MAPK signaling pathways and through subsequent upregulation of p53, and cleaved caspase-3/caspase-3 and Bax/Bcl-2 protein ratios. Overall, the findings of the present study suggest that targeting Wip1 may be a potential therapeutic avenue for the treatment of human ovarian cancer in the future.