Measuring the quality of life in family caregivers of people in palliative care is essential to document the impact of care on the caregiver. This study aimed to adapt and validate a Latin American-Spanish version of the QOLLTI-F scale in family caregivers of palliative care patients. This study was conducted between May and November 2019 in Medellin, Colombia. We develop three phases: translation and semantic adaptation (n = 17), face and content validity (n = 21), construct validity, internal consistency (n = 208) and test-retest reliability (n = 35). Main family caregivers of stage-IV cancer patients receiving palliative treatment, participated. In the translation and semantic adaptation, some items were adjusted following the caregivers' recommendations. In face validity, Fleiss' Kappa was over 0.65 for family caregivers. In content validity, Fleiss' Kappa ranged from 0.54 to 1 for experts. In construct validity, the original version seven-factor structure did not show appropriate model fit indices. The data revealed instead a new 3-factor structure related to (1) impact of care-giving, (2) social and healthcare interactions and (3) meaning of life. Cronbach's alpha was 0.83 for the overall scale. Test-retest reliability was 0.87 between measurements 1 and 2. This study found that The Latin American-Spanish version of the QOLLTI-F scale is an understandable, useful, and relevant tool for family caregivers of people with cancer receiving palliative care. Future research is needed to confirm the factor structure identified in this study.