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Background Molecular biology play a important role in the pathogenesis of malignant tumor.The CacyBP/SIP protein (Calcyclin binding protein and interacting protein) was originally discovered in Ehrlich ascites tumor cells.The function of CacyBP/SIP were described in cellular processes such as ubiquitination, proliferation, differentiation, tumorigenesis, cytoskeletal rearrangement or regulation of transcription.Recent results obtained for a wide range of cancer tissues showed that CacyBP/SIP is expressed in all kinds of tumors investigated.CacyBP/SIP is mainly present in the cytoplasm.The level of CacyBP/SIP expression seems to be correlated with tumorigenesis,invasion and metastasis.Methods 21 tissue arrayers were constructed which contain 1072 cases of gastric cancer and 1072 cases of matched normal tissues.Immunohistochemistry was applied to detect the expression of CacyBP/SIP and to observe the disparation between them.It was evaluated that the relationship of CacyBP/SIP expression and the clinical pathologic characteristics,including tumor size, nerve invasion,primary tumor invasion, metastasis of lymph node, tumor stag-ing, and histology grading.We also studied expression of CacyBP/SIP and other factors which probably influencing patient survival,such as age, tumor location ,tumor size, nerve invasion, gastric wall invasion, lymph node metastasis, differentiation ,(TNM) stage, anemia.Results 21 tissue arrayers contain 1072 and 1072 sites respectively.The positive expression of CacyBP/ SIP is present in the cytoplasm of tumor and nomal cells.The expression of tumor tissue and normal tissue by IHC were 48.6% and 79.4%, respectively.There was significant difference between both expression.There was not close relation between The expression of CacyBP/SIP and tumor size or nerve invasion(P>0.05).But we observed the significant relationship between CacyBP/SIP and primary tumor invasion, metastasis of lymph node, tumor stage and histology grading(P<0.05).Except tumor size and anemia, CacyBP/SIP expression and other items all obviously influenced patient survival,such as age, tumor location, nerve invasion, gastric wall invasion, lymph node metastasis, differentiation ,(TNM) stage.(P<0.05) Conclusions CacyBP/SIP expression was a common event in gastric cancer and normal tissue.The expression level in normal tissue was higher than in tumor tissue.Overexpression of CacyBP/SIP was associated with primary tumor invasion (Tis/T1/T2) , metastasis of lymph node(None), tumor stage (0/Ⅰ/Ⅱ) and histology grading(Well/Moderately-differentiated).CacyBP/SIP expression was independent prognostic factors for gastric cancer The up-regulation of CacyBP/SIP expression was the important inhibitor in gastric cancer development,progression and metastasis.CacyBP/SIP signaling could be a promising new molecular target for designing novel preventive/therapeutic strategies to control this malignancy.