Objective:To observe the expression of phosphorylated mammalian target of rapamycin(p-mTOR),epidermal growth factor receptor(EGFR),growth factor receptor-bound protein 2(Grb2) and vascular endothelial growth factor(VEGF) in human colorectal cancer tissues and to explore their roles in the carcinogenesis of colorectal cancer.Methods: Tissue microarray containing 185 colorectal cancer tissues was constructed and the expression of EGFR,Grb2,p-mTOR and VEGF in the colorectal cancer tissues and the corresponding adjacent tissues was examined by immunohistochemistry methods.The relationship between their expression with the clinicopathological characteristics such as age,sex,invasion depth,lymphatic metastasis,clinical stage and differentiation degree was analyzed.Results: EGFR,Grb2,p-mTOR and VEGF were scarcely expressed or absent in the corresponding adjacent tissues; their positive rates in the colorectal caner tissues were 21.1%,44.9%,42.2% and 54.1%,respectively,which were significantly higher than those in the corresponding adjacent tissues(P<0.05). The expression of EGFR,Grb2,p-mTOR and VEGF was not correlated with the patients’ sex,age and differentiation degree of cancer.Over-expression of EGFR was found significantly associated with the invasion depth and clinical stage of cancer(P<0.05); and over-expression of p-mTOR and VEGF was significantly associated with lymphatic metastasis,invasion depth and clinical stage(P<0.05).There was a correlation between every two of the four proteins (r=0.245-0.567,P<0.05).Conclusion: Over-expression of EGFR,Grb2,p-mTOR and VEGF is closely associated with the development and progresssion of colorectal cancer,and they may be worth further studying as new targets for the molecular target therapy of colorectal cancer.