Objective Living the final days of life being cared for at home is a preference expressed by many. The data on the effectiveness of home-based end-of-life care (EoLC) intervention to improve the holistic conditions of terminally ill patients are scanty. This study sought to evaluate a psychosocial home-based EoLC intervention for terminally ill patients in Hong Kong. Methods A prospective cohort study was conducted, applying the Integrated Palliative Care Outcome Scale (IPOS) at 3 timepoints (service intake, 1-month, and 3-months after enrollment). A total of 485 eligible, consenting terminally ill people (mean age = 75.48, SD = 11.39) were enrolled, with 40.21% (n = 195) providing data at all 3 timepoints for this study. Results Decreasing symptom severity scores were observed for all IPOS psychosocial symptoms, and most physical symptoms, over the 3 timepoints. Improvements in depression and practical concerns had the highest omnibus time effects ( F > 31.92, P < .01) and T0 to T2 paired comparison effects ( Cohen's d > 0.54, P < .01). Physical symptoms of weakness/lack of energy, poor mobility, and poor appetite also showed significant improvements at T1 and T2 ( Cohen's d: 0.22-0.46, P < .05). Bivariate regression analyses showed that improvements in anxiety, depression, and family anxiety were associated with improvements in physical symptoms of pain, shortness of breath, weakness/lack of energy, nausea, poor appetite, and poor mobility. Patients’ demographic and clinical characteristics were not associated with changes in symptoms. Conclusions The psychosocial home-based EoLC intervention effectively improved the psychosocial and physical status of terminally ill patients, irrespective of their clinical characteristics or demographics.