Abstract: Cancer‑related sarcopenia is mainly characterized by protein degradation and muscle depletion caused by catabolism, leading to a decrease in the quality, strength, and function of skeletal muscles. Pancreatic cancer has the highest incidence of cancer‑associated sarcopenia. More than 80% of pancreatic cancer patients have the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, which promote the progress of sarcopenia. The authors systematically elaborate the interaction mechanism between KRAS‑mutant pancreatic cancer and sarcopenia, mainly in four aspects: (1) KRAS driven metabolic reprogramming leads to depletion of muscle energy reserves, affecting the redistribution of muscle fiber energy and resulting in unidirectional energy flow for cancer cell proliferation. (2) By altering the cytokine profile, activating the ubiquitin protease system and the autophagy lysosome pathway, the cancer cells promote myotube degradation, inhibit muscle regeneration, disrupt muscle homeostasis, and lead to unidirectional flow of nutrients to support tumor growth. (3) Oxidative stress caused by cancer cells damages skeletal muscles. (4) Cancer cells induce immune cell remodeling in skeletal muscle. Meanwhile, the authors review the treatment progress of KRAS‑mutant pancreatic cancer‑related sarcopenia. With the deepening research of KRAS‑mutant pancreatic cancer‑related sarcopenia, targeted therapy and personalized intervention are expected to become important means to improve the prognosis and quality of life of patients.