OBJECTIVE: To observe expression of human epidermal growth factor receptor 2 (HER-2) and lung resistance protein (LRP) in tumor tissues of patients with gastric cancer and to explore the relationship between HER-2–mediated gastric cancer resistance and LRP expression. STUDY DESIGN: Immunohistochemical method was applied to test HER-2 and LRP expression in 65 specimens of gastric cancer and 32 non–gastric cancer patients. Western blot was used to examine the phosphorylation state of HER-2 in non–gastric cancer patients and in gastric cancer patients with or without lymphatic metastasis. RESULTS: HER-2 and LRP expression of patients with gastric cancer had no obvious correlation with patient age, gender, tissue differentiation degree, and infiltration depth. The research results showed that HER-2 and LRP expression in gastric cancer tissues presented positive correlation (r=0.335, p<0.05). Phosphorylation of HER-2 was highest in patients with gastric cancer and lymphatic metastasis and higher in patients with gastric cancer only, as compared to that in non–gastric cancer patients. CONCLUSION: LRP may be one of the resistance proteins causing primary resistance of gastric cancer. Activation of HER-2 may mediate gastric cancer resistance through influencing LRP expression. © Science Printers and Publishers, Inc.