Patients with liver metastasis of colorectal cancer (CRC) experience important lifestyle changes that impair the quality of life (QoL). The use of instruments is important to assess the cancer patients’ QoL. To develop a Brazilian translation of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Colorectal Liver Metastases (QLQ-LMC21) questionnaire, and to investigate psychometric validity in patients with CRC with liver metastases, patients with liver metastasis from CRC answered the Brazilian versions of EORTC core Quality of Life Questionnaire-Core 30 (QLQ-C30) and the QLQ-LMC21 module, a demographic data questionnaire and a questionnaire to assess understanding against the translated QLQ-LMC21. Data collection was performed in three Southern hospitals in Brazil, from August 2017 to August 2019. Descriptive analyses and Spearman’s correlation tests were performed for construct and criterion validity. The Cronbach’s alpha test was performed to assess reliability. Significant values were p < 0.05. Ten patients participated in the study for the pilot test and 106 for validation, with a mean age of 58.2 + 12.4 years old. The translated questionnaire was easy to understand for the participants in the pilot test phase, with no need for modification. In the validation of the convergent construct, all the correlations were significant (p < 0.001) and with coefficients above 0.53. In the discriminant validity, among items of different scales, the values of the divergent correlations were pain scale (0.005 to 0.186) and fatigue (−0.01 to 0.186), all non-significant. In the criterion validation, the correlations were significant, p < 0.05, and higher among similar scales of the QLQ-LMC21 and QLQ-C30, p-value < 0.001. The total internal consistency of the questionnaire was adequate, with a Cronbach’s alpha value of 0.790. The Brazilian version of the QLQ LMC21 proved to be a valid reliable questionnaire to be used in conjunction with the QLQ-C30.