Dysfunction of the immune system in colorectal cancer (CRC) can be due to a number of reasons including apoptosis of tumour infiltrating lymphocytes (TILs). The aims of this study were to characterize, phenotypically, the apoptosis of TILs in CRC, and define the association of these findings with prognostic indicators. We used double immunohistochemistry to assess the apoptosis of T-cell subsets. Monoclonal antibodies to T lymphocytes, T helper cells, cytotoxic T cells (CTLs), natural killer cells (NK), CD45 and CD45RO were used. Antibodies against cleaved caspase-3 as a marker of apoptosis were used. Apoptosis of T-cell subsets was detected in the immune infiltrate in CRC. Apoptosis of T lymphocytes showed significant correlation with lymphatic metastasis (P = 0.01), Dukes' stage (P = 0.019). Apoptotic T helper cells showed significant correlation with metastasis (P = 0.04), lymphatic metastasis (P = 0.02), death (P = 0.04) and recurrence (P = 0.04). For apoptosis of CTLs, there was a significant correlation with histological classification (P = 0.02), lymphatic metastasis (P = 0.04), vascular metastasis (P = 0.03) and lymph node metastasis (P = 0.04). A significant association was found between the apoptosis of NK cells and the histological classification (P = 0.04). A significant association was found between the apoptosis of cd45RO cells and the histological classification (P = 0.04). In conclusion, apoptosis of lymphocytes provides theoretical foundation for metastasis and counterattack of colon cancer.