The study aimed to identify mitochondria-related genes (MRGs) in cerebral infarction (CI) and benign prostatic hyperplasia (BPH), which are common conditions in middle-aged and elderly individuals. Researchers analyzed transcriptomic data from public databases and identified eleven candidate mitochondrial genes. Using machine learning, eight hub genes were selected: HSDL2 and PDK4 were downregulated in BPH, while CYP1B1, GYG1, HSDL2, MXD1, SLC22A4, and TNFSF10 were upregulated in cerebral infarction. Nomograms constructed based on these genes showed strong predictive ability for the risk of developing both diseases. RT-qPCR confirmed that HSDL2 and PDK4 expression was significantly lower in patients with both conditions compared to healthy controls. The study provides new research directions for the diagnosis and treatment of BPH and CI.