Background: The study was conducted to validate the Vietnamese version of the European Quality of Life Questionnaire 32 in the Vietnamese community with cancer. Methods: The descriptive design was used to collect data of 367 cancer patients with cancer. The data collection was conducted in four hospitals in Vietnam including the National Lung Hospital, the Oncology Department of Nam Dinh General Hospital, Nghe An Oncology Hospital (49 patients) and the Oncology Department of Lam Dong General Hospital. Participants were hospitalized patients between November 2021 and April 2022. Results: Among types of cancers, the lung cancer accounted the highest prevalence rate (83.4%). The analysis of confirmatory factor was used to confirm the construct validity. The results indicated that the culturally appropriate model fit for Vietnamese individuals with cancer, as indicated by the Chi-Square/df value of 2.330, goodness-of-fit index of 0.896, comparative fit index of 0.890, and root mean square error of approximation of 0.060. The instrument demonstrated good reliability, with Cronbach's alpha ranging from 0.731 to 0.808 and MacDonald's omega ranging from 0.722 to 0.804. Conclusion: The EORTC QLQ-SWB32 questionnaire was reliable and suitable using for Vietnamese population for assessing the quality of life of cancer patients. The Vietnamese version of the EORTC QLQ-SWB32 can be used as a valuable tool in measuring and addressing the spiritual well-being of cancer patients, even in the face of a potentially fatal illness.