BACKGROUND AND AIMS: The immune cells in tumor microenvironment release chemokines and cytokines which determine the immune phenotype of the tumor and play an important role in the prognosis. Present study evaluates the gene expression levels of IL-21 and IL-32 and their relations to clinicopathologic parameters in colorectal cancer. PATIENTS AND METHODS: 31(17F) patients with colorectal cancer were included. Samples were obtained from normal and tumor tissues. After RNA isolation, IL-21 and IL-32 gene expression levels were measured. Immunohistochemistry was also carried out for CD4+, CD8+ and NKcells to measure cell density. The relations between expression levels, immune cell density and differentiation, stage, presence of vascular, perineural invasion and lymph node metastasis(MLN) were investigated. RESULTS: IL-32 gene expression levels were increased in tumor tissues. IL-21 levels were found to be decreased in 50% of the patients. IL-32 levels were also increased with the stage however, it was decreased significantly with the increased number of the MLN. On the other hand, expression levels of IL-21 increased significantly with the presence of vascular invasion. CD4+ density was decreased with increased T-stage, vascular invasion whereas CD8+ density decreased only with the vascular invasion. CONCLUSIONS: IL-32 expressed by tumor microenvironment reveals that expression increased to control tumor growth, but levels are decreased with the increased number of MLNs which might be due to decreased CD4+ cell density. Changes on IL-21 and IL-32 together with the changes on immune cell density, indicate their role in tumor growth and invasion in colon cancer.