Abstract: Objective To explore the correlation between the expression of secreted protein acidic and rich in cysteine(SPARC) and the prognosis of postoperative patients with esophageal squamous cell carcinoma(ESCC). Methods Eighty-nine postoperative patients with ESCC treated in the Affiliated Cancer Hospital of Zhengzhou University were included in the investigation. The expression of SPARC protein was detected in ESCC specimen and normal esophageal mucosa by immunohistochemistry method. The relationship of SPARC protein expression with patients' clinical characteristics and prognosis was analyzed statistically. Results The expression of SPARC protein was significantly up-regulated in ESCC sample compared with normal esophageal mucosa (65.17% vs. 8.00%, P=0.000), and predominately located in tumor stroma. SPARC protein expression was negatively correlated with lymph node metastasis (OR=0.369, P=0.038) while it was not related with gross morphology, differentiation grade or other clinical characteristics. Postoperative patient survival was not associated with SPARC protein expression (HR=0.80, P=0.691), but it was related with tumor site (HR=0.34, P=0.037), differentiation grade (HR=4.12, P=0.000) and stage (HR=6.36, P=0.017). Conclusion SPARC protein dominantly expresses in the stroma of ESCC. It is negatively related with lymph node metastasis and does not display the association with the prognosis of postoperative ESCC patients.