Introduction: People with colorectal cancer (CRC) can present adverse effects, impairing the quality of life related to health (HRQoL). Objective: To validate the QLQ-CR29 module for the assessment of HRQoL, in Chile. Materials and method: Cross-sectional study that included 170 people with CRC. The internal consistency and construct validity (hypothesis tests) were analyzed. Results: 117 patients (68.8%) were evaluated before surgery and 53 (31.2%) after tumor resection. The internal consistency of the QLQ-CR29 was α = 0.838. The proposed hypotheses were confirmed: The patients evaluated before surgery complained more of “blood/mucus in the stool”, “abdominal pain”, “hair loss” and “abdominal swelling”, while the patients evaluated after presented more “fecal incontinence” (p < 0.05). Before surgery, patients with rectal cancer presented higher values of “urinary frequency”, “frequency of stools”, “pain in the buttocks”, “taste problems” and “embarrassment”; while those with colon cancer complained more of “blood/mucus in stool” (p < 0.05). After surgery, patients with CCR had higher “stool frequency”, “flatus” and “embarrassment” (p = 0.004) compared with those with colon cancer (p < 0.05). Ostomized patients presented more “fecal incontinence” and “embarrassment” (p < 0.001). Low significant correlations were observed between most of the dimensions of the QLQ CR29 with the dimensions of the QLQ C30. Con-clusion: The Chilean version of the QLQ CR29 module is adequate to assess HRQoL in people with CRC.