Background: The mini-suffering state examination is a valid and reliable measure that have been used to assess suffering in patients with advanced cancer. The aim of this study was to carry out a psychometric analysis of the Spanish version of the mini-suffering state examination. Method: A validation study was conducted. Seventy-two informal caregivers of deceased patients in palliative care were included in this study. A psychometric testing of content validity, internal consistency, and convergent validity with the Spanish version of the quality of dying and death questionnaire was performed. Results: The original instrument was modified to be used by informal caregivers. The content validity was acceptable (0.96), and the internal consistency was moderate (α = 0.67). Convergent validity was demonstrated (r = −0.64). Conclusion: The Spanish modified version of the MSSE showed satisfactory measurement properties. The Spanish modified version of MSSE can be useful to facilitate screening, monitor progress, and guide treatment decisions in end-of-life cancer patients.