OBJECTIVE: To study p53 up-regulated modulator of apoptosis (PUMA) and bcl-2 interacting mediator of cell death (BIM) of the BH3-only protein family expression in colorectal cancer tissues and its relationship with colorectal cancer invasion, metastasis and prognosis. METHODS: Immunohistochemical staining (EnVision) was used to detect PUMA/BIM expression in 30 cases of normal mucosa, 30 cases of colorectal adenoma and 142 cases of colorectal cancer tissues. RESULTS: PUMA in colorectal cancer tissues was positive expressed (82.4%), which was significantly lower than in the normal mucosa colorectal adenomas (96.7%) and normal mucosa tissues (96.7%) (both χ(2) = 3.93, P < 0.05). Positive expression rate of BIM in colorectal cancer tissues (62.7%) was significantly lower than that in colorectal adenomas and normal mucosa (96.7% and 90.0%) (χ(2) = 8.42 and 13.29, P < 0.01). PUMA and BIM in colorectal cancer tissues were positively correlated (r = 0.747, P = 0.000). PUMA expression was related to tumor differentiation (χ(2) = 11.87), invasion depth (χ(2) = 11.59), lymph node metastasis (χ(2) = 12.82), TNM stage (χ(2) = 33.47) and P-gp expression (χ(2) = 18.30), all P < 0.05, but not related to the patients' age, gender, tumor size, tumor histological type and GST-π expression (P > 0.05). BIM expression was related to tumor differentiation (χ(2) = 16.19), lymph node metastasis (χ(2) = 14.95), TNM stage (χ(2) = 52.66) and P-gp expression (χ(2) = 10.60) (P < 0.05), but not related to patients' age, sex, tumor size, tumor histological type, invasion depth and GST-π expression (P > 0.05). 1-, 3-, 5-year survival rates of the positive expression of PUMA/BIM in patients with colorectal cancer were significantly higher than that of PUMA/BIM in patients with negative expression (χ(2) = 6.10 and 27.6, P < 0.05). Cox multivariate analysis showed that lymph node metastasis (RR = 0.238), TNM stage (RR = 7.895), PUMA (RR = 1.691) and BIM (RR = 0.440) could be used as independent prognostic indicators (P < 0.05). CONCLUSIONS: PUMA and BIM expressions in colorectal cancer are related to the tumor invasion, metastasis and prognosis. Low expressions of PUMA and BIM were related to the late period and poor prognosis of colorectal cancer patients.