Abstract: Objective To investigate the role of secreted protein acidic and rich in cysteine(SPARC)in invasion,metastasis of esophageal squamous cell carcinoma(ESCC). Methods The differential protein expression of SPARC between esophageal squamous cell carcinoma and its corresponding normal esophageal mucosa was detected by immunohistochemistry(IHC) analysis.And the relationship between the expression of SPARC and invasion,metastasis was analyzed. Results Positive expression(+/++) of SPARC protein was detected in one hundred sixty-two cases, and negetive expression(-) was detected in 38 cases.The expression of SPARC protein was significantly upregulated in ESCC compared to that in corresponding normal esophageal mucosa(P<0.01).SPARC was positive expression in tumor stromal in most cases.High levels of SPARC in tumor cytolymph could be seen in few cases(21 cases).And the immunoactivity was detected mainly in the cancer cells localized at the tumor-stroma interface.SPARC protein expression and stage,metastasis was correlated significantly(P<0.05).The SPARC protein expression was higher in patients with later stages metastasis,and was not related with gender,age,differentiation,depth of invasion,related habits (drinking,eating pickled foods,etc.),family history,etc(P>0.05). Conclusion SPARC expression as a marker can be used to predict stage and metastasis of ESCC.