To explore the changes in gastrointestinal hormone levels and gastric duodenal mucosal structure in tumor cachexia model mice.20 mice were randomly divided into a blank group and a model group. The model group established a tumor cachexia animal model through lung cancer in situ transplantation, and observed changes in body mass, lung mass, hemoglobin, serum total protein, serum albumin, serum pepsinogen, serum ghrelin, and gastric duodenal mucosa. On the 18th day of the experiment, the body weight of the model group mice was 14.21 g±1.19 g, which was lower than that of the blank group 19.09 g±0.63 g, with statistical differences (P<0.001). The lung mass of the model group mice was 0.17 g±0.05 g, which was higher than that of the blank group 0.14 g±0.02 g, with no statistical difference (P>0.05). The hemoglobin, serum albumin, and total serum protein of the model group mice were 92.10±27.13 g/L, 14.69 g/L±3.29 g/L, and 33.09 g/L±7.11 g/L, respectively, all lower than those of the blank group at 129.40 g/L±29.47 g/L, 33.75 g/L±4.26 g/L, and 69.94 g/L±8.45 g/L, with statistical differences (P<0.01). The serum levels of pepsinogen and serum ghrelin in the model group mice were 54.85 ng/mL±4.18 ng/mL and 4292.34 ng/mL±431.57 ng/mL, respectively, which were lower than those in the blank group at 72.18 ng/mL±6.94 ng/mL and 5469.26 ng/mL±482.357 ng/mL, respectively, with statistical differences (P<0.01). The model group of mice had incomplete gastric and duodenal mucosa, damaged and shortened villus structure, and unclear mucosal muscle layer structure. Damage to the gastric and duodenal mucosa and decreased secretion of gastrointestinal hormones are important components of the pathogenesis of tumor cachexia, and also reflect the theoretical idea of traditional Chinese medicine that “the spleen and stomach are the source of qi and blood biochemistry”.