Spiritual care for patients’ quality of life (QOL) and hope should be included in home medical care for patients with limited life expectancy. This study aimed to analyze the associations between estimated life expectancy, QOL, and hope among patients receiving home medical care in Japan. This multicenter cross-sectional study involved 29 home medical care facilities in Japan. Patients were categorized by estimated life expectancy, as assessed by home medical care physicians. The outcomes were QOL measured via the Quality-of-Life Scale for Elderly Patients Receiving Professional Home Care (QOL-HC: higher score indicates better QOL), the domain scores of health-related hope (“health,” “role and connectedness,” and “something to live for”; higher scores indicate higher levels of hope), and life functioning measured using the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0; higher score indicates worse functioning and disability). QOL-HC scores were significantly higher in patients with shorter life expectancy (< 6 m vs. ≥ 1 y, adjusted mean differences: 0.7 points [95%CI 0.1 to 1.3]). Regarding health-related hope, “something to live for” scores were associated with shorter life expectancy (< 6 m vs. ≥ 1 y, -17.7 points [-34.2 to -1.2]), whereas “role and connectedness” scores did not change remarkably with shorter life expectancy (< 6 m vs. ≥ 1 y, -3.3 points [-16.4 to 9.8]). Furthermore, shorter life expectancy was associated with higher WHODAS 2.0 scores (< 6 m vs. ≥ 1 y, 19.6 points [4.3 to 34.8]). Home medical care physicians who engage in spiritual care should facilitate thoughtful dialogue with their patients by recognizing declines in life functions and hope for fulfilment, which are associated with short life expectancy.