ObjectivesTo translate and validate the Thai Self-Care of Chronic Illness Inventory version 4.c (Thai SC-CII v4.c) in individuals with chronic illnesses. MethodsA scale translation and cross-sectional validation study was conducted. The English version was translated for Thai involved nine steps: preparation, forward translation, reconciliation, back-translation, back-translation review, harmonization, cognitive debriefing, review of cognitive debriefing and finalization, and proofreading. A cross-sectional study was conducted from July to November 2022 at 16 primary care centers in southern Thailand, involving 410 participants with at least one chronic condition. Validity assessments included structural, convergent, and discriminant validity. Concurrent validity examined correlations between SC-CII v4.c with the Self-Care Self-Efficacy Scale (SCSES) and self-perceived health. Internal coherence reliability was calculated using Cronbach’s α coefficient, item-total correlation coefficients, and the composite reliability (CR) index. ResultsThai SC-CII v4.c demonstrated excellent translational validity (κ = 0.99). The specified Self-Care Maintenance model fit well, with minor differences in health promoting behavior and illness-related behavior items compared to the original model. The original Self-Care Monitoring, and Self-Care Management models fit well with Thai data. Simultaneous confirmatory factor analysis confirmed a satisfactory fit of the full SC-CII v4.c. Convergent validity had partial support (average variance extracted = 0.23–0.51), and discriminant validity was established (heterotrait-monotrait ratios = 0.37–0.88). Concurrent validity was supported by positive correlations between each scale and overall SC-CII v.4c with SCSES (r = 0.25–0.65) and self-perceived health (r = 0.09–0.35). The Cronbach’s α coefficient were adequate for all scales except the Self-Care Maintenance scale (Cronbach’s α = 0.68), but the CR estimate improved the reliability of all three scales (ranging 0.80–0.82). All items had satisfactory item-total correlation coefficients (ranging 0.34–0.71), except the one pertaining to sleep. ConclusionsThe Thai SC-CII v4.c is valid and reliable for assessing self-care in various chronic illnesses. Further testing is recommended for patients with specific diseases.