The aim of this study is to investigate the expression of AP-4, VEGF, and MMP-9 genes in human colorectal cancer. The expression pattern of activator protein-4 in 160 colorectal cancer compared with 32 colorectal adenomas and 32 normal colorectal tissues is demonstrated by tissue microarray-immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction. Apoptosis status using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling by comparing activator protein-4 positive versus activator protein-4 negative colorectal cancer is also assessed. The messenger RNA levels of vascular endothelial growth factor and matrix metalloproteinase-9 expression in activator protein-4 positive and negative colorectal cancer were measured using real-time reverse transcriptase- polymerase chain reaction. The activator protein-4 expression in normal colorectal tissue, adenoma, and adenocarcinoma were 4 of 32, 8 of 32, and 78 of 160, respectively. It is shown that the activator protein-4 expression was significantly correlated with the progression of colorectal cancer (P < .01) and differentiation and lymph node metastasis (P < .01). Our results also presented that the activator protein-4 expression was associated with the expression of matrix metalloproteinase-9 and vascular endothelial growth factor in the advanced colorectal cancer.