Background: While self-care is known to influence well-being in chronic illness, its specific role during chemotherapy—particularly within unique cultural contexts like Turkey—remains underexplored. Purpose: This study examined the relationship between self-care behaviors and psychological well-being (PWB) in Turkish chemotherapy patients and assessed self-care's predictive power on PWB. Methods: A cross-sectional study was conducted with 403 chemotherapy patients from a university hospital using convenience sampling. Data were collected using the Self-Care Adequacy and Needs Level Scale (SCANS-Chemo) and Psychological Well-Being Scale. Results: Patients demonstrated moderate self-care levels (Mean = 80.69 ± 22.94) and PWB (Mean = 35.63 ± 12.84). A very strong positive correlation was found between self-care and PWB (r = .917, p < .001). Higher self-care scores significantly predicted better PWB (β = .58, p < .001), explaining 32% of variance. Key factors associated with better outcomes included higher education, male gender, and recent chemotherapy initiation. Conclusion: Self-care behaviors are a significant predictor of psychological well-being in chemotherapy patients. Healthcare professionals should develop culturally-tailored self-care interventions to enhance patients' psychological well-being during treatment. Implications for Nursing: Clinical practice should incorporate structured self-care assessments, personalized self-care training focusing on activity maintenance and sleep regulation, and regular monitoring of patients' self-care capacity throughout chemotherapy treatment.