Cancer is a major cause of mortality and a leading driver of healthcare costs, ranking second in total medical expenditure in South Korea. Although hospice and palliative care improve quality of life and reduce costs, comparative evidence on end-of-life medical costs across hospice settings in Korea remains limited. Therefore, a comprehensive evaluation of hospice cost-effectiveness is needed to inform healthcare resource allocation.To compare end-of-life medical costs among cancer patients across home-based hospice, inpatient hospice, and general ward settings, and to assess cost differences according to place of death.This retrospective study analyzed medical records of 1,261 cancer patients who died at a single tertiary institution between January 1 and December 31, 2022. Medical expenses were evaluated for the final 1, 3, 6, and 12 months of life using SAS 9.4. Patients were categorized into hospice and non-hospice groups; hospice users were further divided into home-based and inpatient hospice subgroups, with the home-based group additionally classified as home-death or ward-death. Secondary analyses excluded patients who died within seven days of hospice admission to minimize underestimation of hospice-related costs.Hospice users showed more than 50% lower total medical expenditures than non-hospice users across all periods (p < 0.05). After excluding patients who died within seven days of hospice admission, home-based hospice care consistently incurred lower costs than inpatient hospice (p < 0.05). Furthermore, home deaths were associated with reduced expenses compared with ward deaths, except during the 12-month pre-death interval (p < 0.05).These findings provide quantitative evidence that hospice care—particularly home-based services—significantly reduces the economic burden at the end of life. The results are consistent with international evidence showing that early hospice referral and community-based palliative care, by maintaining continuity outside hospitals, are associated with lower costs.Hospice care substantially reduces end-of-life medical expenses for cancer patients, with the greatest savings observed in home-based and home-death settings. Early hospice referral and the expansion of home-based palliative services may enhance cost-effectiveness and promote patient-centered end-of-life care for cancer patients.