Obstructive sleep apnea (OSA) is a common sleep disorder characterized by recurrent upper airway obstructions, leading to substantial health burdens and socioeconomic costs. This study aimed to identify Hypoxia and Mitophagy-Related Differentially Expressed Genes (HMRDEGs) and evaluate their potential as biomarkers and therapeutic targets for OSA. Transcriptomic data from GSE135917 and GSE38792 in the GEO database were analyzed using the limma package to identify differentially expressed genes (DEGs), which were subsequently intersected with hypoxia- and mitophagy-related gene sets(HMRGs) curated from GeneCards and PubMed. A total of 24 HMRDEGs were identified, and four hub genes-NLRP3, MAPK9, RBBP4, and CLINT1-were used to construct a diagnostic model that demonstrated excellent discrimination (AUC = 0.982 in the training set and 0.812 in the validation set). Gene Ontology and KEGG analyses linked these genes to protein catabolism and autophagy pathways, while immune-cell infiltration profiling associated them with specific leukocyte subsets. Collectively, our findings underscore hypoxia-mitophagy crosstalk as a central mechanism in OSA and present a robust biomarker panel with therapeutic potential.