Objective:To investigate the influence of chemotherapy on the phenotype of secreted protein, acidic and rich in cysteine (SPARC) in gastric cancer (GC). Methods:Immunohistochemistry was used to analyze SPARC expression in 132 GC patients. Among these patients, 54 with preoperative chemotherapy and 78 without preoperative chemotherapy were selected to analyze the effect of chemotherapy on SPARC phenotype by comparing the postoperative specimens of the two cohorts. Results:SPARC expression was higher in GC lesions than in the desmoplastic stroma surrounding the tumor cells and noncancerous tissues. High SPARC expression was related to invasion depth, lymph node metastasis, and TNM staging. SPARC expression was lower in patients with preoperative chemotherapy than in controls ( P<0.05). Gross type, histology, depth of invasion, lymph node metastasis, TNM staging, and SPARC phenotype correlated with the overall survival of the patients with preoperative chemotherapy. Further multivariate analysis suggested that lymph node metastasis, histology, and SPARC phenotype after chemotherapy were independent prognostic indicators of GC. Conclusion:SPARC expression was associated with invasion depth, lymph node metastasis, TNM staging and GC prognosis. Preoperative chemotherapy may change the phenotype of SPARC in GC patients.