Objective:To investigate the expression of glucose regulated proteins GRP78 and GRP94 in human colon cancer.Methods:Tissues of resected primary colon cancer, colon adenoma and normal tissue were investigated. Protein expression was detected with immunohistochemical staining, mRNA expression levels of GRP78 and GRP94 were determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) after mRNA extraction. Results:The expression of GRP94 and GRP78 was significantly higher in colon cancer when compared to those in colon adenoma and normal tissue (P<0.01). GRP94 mRNA and protein expression was found to be in close relationship with the grade of differentiation, Dukes stages, lymph node involvement and remote metastasis in colon cancer (P<0.01), but no relationship with gender and age (P0.05). GRP78 mRNA and protein expression increased with cancer progression along the normal tissue-adenoma-cancer sequence, but showed no association with grade of differentiation, Dukes stages, lymph node involvement, remote metastasis, gender and age (P0.05). The mRNA expression of GRP78 and GRP94 was consistent with the proteins (P<0.01), but there is no correlation between overexpression of GRP78 and GRP94 (P0.05), and the patients with both strong GRP78 and GRP94 protein expression did not show advanced tumor stages (P0.05). Conclusion:Overexpression of GRP78 and GRP94 was found in colon cancer. Overexpression of GRP94 was closely related to cellular differentiation, Dukes stages, invasion and metastasis.