Hypoxia-inducible factor-1alpha (HIF1α) is crucial in varicocele-induced oxidative stress and apoptosis, and we found that PI3K/Akt, mTOR, and HIF-1 signaling pathways play an important role in HIF1α expression by enrichment analysis and review of related literature (Babaei et al., 2021), and by constructing the hub targets PPI network, it was found that HIF1α upstream related targets PIK3CA, AKT1, MTOR may be potential core targets for MLST in treating varicocele-associated male infertility. This evidence concerns the gene HIF1A and varicocele.