Objective：To study the gene expression characteristics of renal tubular epithelial cells under oxidative stress caused by caspase-3 inhibitors via screening the potential candidate genes，which will lay the foundation for revealing the mechanism of caspase-3 regulating ROS injury in renal tubular epithelial cells. Methods：The renal tubular epithelial cells HK-2 were treated with H₂O₂ at a final concentration of 300 μmol/L for 6 h，and then randomly divided into control group and caspase-3 inhibitor group(Ac-DEVD-CHO， 15 μmol/L). The sequencing was completed by using the Illumina Hiseq 2500 platform. Enrichment analysis and an interaction network were performed to screen differential genes. Quantitative PCR was used to verify the first 10 differentially expressed genes (DEGs). The HK-2 cells treated with H₂O₂ (300 μmol/L)for 6 h were then divided into control group，caspase-3 inhibitor group (Ac-DEVD-CHO，15 μmol/L)，CTNNB1 group(pcDNA3.1(+)-CTNNB1)，caspase-3 inhibitor+CTNNB1 group(Ac-DEVD-CHO， 15 μmol/L+pcDNA3.1(+)-CTNNB1)and caspase -3 inhibitor+CTNNB1 NC group(Ac -DEVD -CHO，15 μmol/L+pcDNA3.1(+)- CTNNB1 NC)randomly. MTT assay was used to detect cell proliferation，flow cytometry was used to detect cell apoptosis and ROS level，Western blot was used to detect apoptosis-related proteins. Results：A total of 185 DEGs were selected in the control group and the caspase-3 inhibitor group. Quantitative PCR showed FIS1，EZR，COL7A1，RPL5，MAP4，CEBPB and CTNNB1 mRNA were lowly expressed(all P ＜ 0.05)and SNRPB mRNA was highly expressed in caspase-3 inhibitor group(P ＜ 0.05). The proliferation was higher in the caspase -3 inhibitor group and was lower the CTNNB1 group compared to the control(both P ＜ 0.05). The proliferation of the caspase-3 inhibitor+CTNNB1 group was lower than that of the caspase-3 inhibitor group(P ＜ 0.05)，but still higher than the control (P ＜ 0.05). The apoptosis and the expression of cleaved-caspase-3 and cleaved-PARP were lower in caspase-3 inhibitor group and were higher in CTNNB1 group compared to the control(both P ＜ 0.05). The apoptosis and the expression of cleaved-caspase-3 and cleaved-PARP in caspase-3 inhibitor+CTNNB1 group were higher than those in the caspase-3 inhibitor group(P ＜ 0.05)，but were still lower than the control(P ＜ 0.05). The ROS in the caspase-3 inhibitor group was lower but was higher in CTNNB1 group compared to that of the control group(P ＜ 0.05). The ROS in the caspase-3 inhibitor+CTNNB1 group was higher than that of the caspase-3 inhibitor group(P ＜ 0.05)，but was still lower than the control(P ＜ 0.05). Conclusion：Aberrant gene expression induced by caspase-3 inhibitor is associated with renal injury under oxidative stress. The injury of oxidative stress on renal tubular epithelial cells is caspase - 3 dependent. Inhibition of caspase-3 has a protective effect on renal injury and CTNNB1 is involved in this process.