OBJECTIVES: Symptom and functional assessment is challenging in geriatric oncology care. This multicenter cross-sectional study examined the use of a multiple-symptom assessment tool, the MD Anderson Symptom Inventory (MDASI), on Chinese patients with cancer aged 65 years and older. METHODS: Patient-rated symptoms and functioning were assessed using MDASI and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire. RESULTS: The most severe symptoms were fatigue and poor appetite. The older group (75-84 years old, n = 224) reported a more severe difficulty remembering (effect size [ES] 0.32; P < .001), shortness of breath (ES 0.20; P = .020), and interference with general activity (ES 0.14; P = .027), with significantly worse physical functioning (ES -0.33; P < .001) and cognitive functioning on the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (ES 0.20; P < .001) than the younger group (65-74 years old, n = 555). For MDASI measures of the core symptoms and total interference with daily activity, Cronbach α coefficients were 0.90 and 0.93, respectively, for the younger group; and 0.93 and 0.94 for the older group, respectively. Moderate to severe (score ≥4) interference with general activity and walking on MDASI accurately indicated poor performance status (area under the curve 0.8089 and 0.7969, respectively) and lack of independence status of Activities of Daily Living (area under the curve 0.7993 and 0.8304, respectively). CONCLUSIONS: MDASI is psychometrically reliable, valid, and clinically sensitive for the measuring symptom burden and functional status of Chinese patients with cancer aged 65 years and older. MDASI could be adopted to measure multiple symptoms and physical functioning outcomes in geriatric oncology practice as well as for research on treatment benefits.