OBJECTIVE: The apoptotic autophagy pathway in premature ovarian failure has received much attention in recent years. To explore the specific mechanism of the effect of acupuncture in the treatment of POF, the group will further investigate the role of genes related to the profiling system. METHODS: In this study, we first searched POF using the databases GEO, GAD, and DigSeE, and then explored the relevant gene functions by enrichment analysis. Also, the association with acupuncture intervention was verified by using the databases DAB and TTD. Next, protein interaction networks were mapped and analyzed using CytoScape 3.2.1 software, the databases STRING and DAVID, which were explored in depth by consensus clustering and regression analysis optimization. Finally, the prediction model was constructed and tested through bibliometrics, confirming that the study is reliable and in good agreement with the conclusions obtained by the current leading researchers. RESULTS: We collated apoptotic autophagy-related genes and found that the mechanism of action of acupuncture intervention in premature ovarian failure may be related to PI3K/Akt-mediated apoptosis and autophagic processes in granulosa cells. CONCLUSION: Analysis of the mechanism of action of acupuncture intervention in premature ovarian failure may be related to the cell proliferation and apoptosis pathway represented by PI3K/Akt, which alters the number of primordial follicles and affects ovarian reserve function through bioactive factor effects during follicular atresia.