Abstract. Background PI3K/Akt signaling has been shown to be activated in a variety of cancers. However, the correlation between Akt activation and VEGF expression is unclear in colon cancer tissues. This study aimed to investigate the expression and predictive value of phosphorylated Akt (pAkt) and VEGF in colon cancer tissues. The expression of PI3K, pAkt and VEGF was detected by immunohistochemical staining in 60 samples of colon cancer tissues and their corresponding adjacent normal colon tissues. In addition, the correlations between the expression levels of the 3 proteins and the clinicopathological parameters of the colon cancer cases were analyzed. The positive rates of PI3K, pAkt and VEGF expression were 71.7% (43/60), 68.3% (41/60) and 61.7% (37/60) in colon cancer, respectively, which were significantly higher than in adjacent normal colon tissues (P<0.001). Correlation analyses showed that PI3K expression was not significantly associated with the gender or age of the patients, tumor size or differentiation (P>0.05), but was closely associated with serous coat infiltration and lymphatic metastasis of colon cancer (P<0.05). Neither pAkt nor VEGF expression were significantly associated with the gender or age of the patients, or tumor differentiation (P>0.05), but were closely associated with tumor size, serous coat infiltration and lymphatic metastasis of colon cancer (P<0.05). In addition, the expression levels of Pl3K and pAkt were positively correlated with that of VEGF in colon cancer tissues (P<0.05). Our data show a positive correlation between PI3K/Akt activation and VEGF expression in colon cancer tissues and indicate that pAkt is an independent prognostic marker for colon cancer patients.