Abstract: Objective To observe the effect of lactoneⅠfrom Atractylodes macrocephala Koidz (LAMK I) on the cytokines and proteolysis-inducing factors (PIF) in cachectic cancer patients. Method Sixty-four cachectic cancer patients were randomized into two groups, namely LAMK I group and FOE (fish oil-enriched nutritional supplementation) treatment group. The appetite, body weight changes, mid-arm muscle circumference (MAMC), and KPS scores were recorded 3 and 7 weeks after the treatment. Immumohistochemistry was used to analyze the changes in the cytokines interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α and Western blotting employed to examine the changes of PIF after the treatment. Results The patients’ appetite and MAMC in LAMKI group was better than those of patients in FOE group, and the serum IL-1 and TNF-α levels and urine PIF level were significantly lower than those of FOE group. Body weight and serum IL-6 level were not significantly different between the two groups. Conclusion LactoneⅠfrom Atractylodes macrocephala Koidz can be beneficial for treating cancer cachexia.