Objective：To investigate the mechanism of olaparib combined with enzalutamide in synergistically inhibiting the growth of prostate cancer cells. Methods：CCK -8 was used to determine the half -inhibitory concentrations of olaparib and enzalutamide in prostate cancer cell line C4-2，as well as the combined index of the two drugs. The effects of the combination of the two drugs on the proliferation and apoptosis of prostate cancer cells were verified by in vitro proliferation，clone formation experiments and flow cytometry. The accumulation of double - strand damagewas observed by immunofluorescence. Next - generation high - throughput sequencing of prostate cancer cells treated with olaparib and enzalutamide in combination and alone was used to explore the mechanism of the synergistic effect of the two drugs. The mRNA and protein expression levels of key genes in the synergistic pathway were detected by qRT - PCR and Western blot. Results：The combination index showed that the combination of olaparib and enzalutamide had strong synergistic effects in prostate cancer cell line C4-2. Compared with the single drug，the combined use of the two drugs significantly inhibited cell proliferation and cell cloning ability. Flow cytometry showed that the combination of the two drugs significantly promoted cell apoptosis compared with the single drug. Immunofluorescence showed that the double - strand damagewas significantly increased after the combination of the two drugs. Analysis of the results of next -generation high -throughput sequencing showed that the combination of the two drugs led to the activation of apoptosis and other pathways. Through the detection of mRNA and protein，it was found that the combination of the two drugs would lead to the high expression of the pro-apoptotic genes TNFAIP2 and TNFAIP8L1，and the low expression of the anti - apoptotic gene TNFAIP8. Conclusion：Olaparib combined with enzalutamide can promote the expression of pro-apoptotic genes TNFAIP2 and TNFAIP8L1 and inhibit the expression of anti-apoptotic gene TNFAIP8 to synergistically promote cell apoptosis and inhibit the growth of prostate cancer cells.