The article reviews the role of acidic extracellular pH in tumor progression. It highlights that the acidic microenvironment, primarily caused by lactate secretion from anaerobic glycolysis, is a significant feature of tumor tissues. Transporters and pumps, such as the Na⁺/H⁺ exchanger, H⁺-lactate co-transporter, monocarboxylate transporters, and the proton pump (H⁺-ATPase), contribute to H⁺ secretion and may be associated with tumor metastasis. An acidic pH activates lysosomal enzymes and induces the expression of pro-metastatic genes through an intracellular signaling cascade distinct from hypoxia. CO₂ from the pentose phosphate pathway is another source of acidity, highlighting the independence and deep association between hypoxia and extracellular acidity. The article discusses the importance of acidic pH in regulating cellular phenotype, immune escape, and metastasis, and explores potential therapeutic strategies targeting these mechanisms.The article reviews the role of acidic extracellular pH in tumor progression. It highlights that the acidic microenvironment, primarily caused by lactate secretion from anaerobic glycolysis, is a significant feature of tumor tissues. Transporters and pumps, such as the Na⁺/H⁺ exchanger, H⁺-lactate co-transporter, monocarboxylate transporters, and the proton pump (H⁺-ATPase), contribute to H⁺ secretion and may be associated with tumor metastasis. An acidic pH activates lysosomal enzymes and induces the expression of pro-metastatic genes through an intracellular signaling cascade distinct from hypoxia. CO₂ from the pentose phosphate pathway is another source of acidity, highlighting the independence and deep association between hypoxia and extracellular acidity. The article discusses the importance of acidic pH in regulating cellular phenotype, immune escape, and metastasis, and explores potential therapeutic strategies targeting these mechanisms.