Second, although puerarin is a non‐targeted natural compound, it binds with high specificity to MIC19—a mitochondrial inner membrane protein critical for cristae integrity and OXPHOS maintenance.[22, 25] Ti‐Tregs rely heavily on mitochondrial respiration rather than glycolysis to sustain their suppressive phenotype in the hostile TME.[13, 26] Our single‐cell transcriptomic analysis of human HCC confirmed that among tumor‐infiltrating lymphocytes, Ti‐Tregs exhibit the highest enrichment of OXPHOS‐related gene signatures. This evidence concerns the gene CHCHD3 and hepatocellular carcinoma.