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Objectives: To evaluate the safety, short-term efficacy and prognostic characteristics of spatially fractionated radiation therapy (SFRT) in patients with advanced or metastatic solid tumors. Methods: Clinical data of patients with advanced/recurrent metastatic malignant tumors who received SFRT in Shenzhen Hospital of Cancer Hospital, Chinese Academy of Medical Sciences from June 2023 to August 2024 were retrospectively analyzed. Patients were divided according to radiotherapy modality into the lattice radiation therapy (LRT) group (high-dose irradiation delivered in a spherical lattice pattern within the target area) and the stereotactic central ablative radiation therapy (SCART) group (ablative dose irradiation delivered to the tumor core area). All patients underwent at least one imaging follow-up after treatment. Results: A total of 49 patients were enrolled; 12 patients who did not complete imaging follow-up were excluded, and finally 37 patients were included in the analysis. The median age was 58 years (range, 28 to 77 years), male accounted for 67.6% (25/37), and the median Eastern Cooperative Oncology Group (ECOG) performance status score was 1 point (range, 1 to 2). The most common primary tumor type was gastrointestinal tumors (48.6%, 18/37). The median number of prior lines of chemotherapy before radiotherapy was 3 (range, 0 to 11). The median maximum diameter of the target area was 9.3 cm (range, 4.9 to 33.4 cm), and the median volume was 236.6 cc (range, 28.6 to 5 053.0 cc). There were 21 cases (56.8%, 21/37) in the LRT group and 16 cases (43.2%, 16/37) in the SCART group. The median SFRT vertex dose was 12 Gy (range, 6 to18 Gy), and the median number of fraction was 5 (range, 1 to 5). A total of 40.5% (15/37) of patients received conventional fractionated radiotherapy or stereotactic body radiotherapy (SBRT) before or after SFRT. Furthermore, 35.1% (13/37) of patients received sequential immunotherapy, with a median of 3 cycles (range, 2 to 4). As of May 16, 2025, the median follow-up time was 13.2 months (range, 9.4 to 22.7 months); 21 patients were alive, 12 died (11 due to tumor progression, 1 due to immune checkpoint inhibitor-related pneumonia), and 4 were lost to follow-up. Efficacy evaluation showed that the median time for first imaging assessment was 3 months (range, 0.5 to 6 months), the in-field disease control rate was 94.6%, and the 6-month in-field disease control rate was 85.0% (17/20). Among the 21 patients with pre-treatment symptoms, pain relief was achieved in 11 patients (11/15), and the overall symptom control rate was 81.0% (17/21). No grade Ⅲ or higher radiotherapy-related acute/chronic adverse events were observed. Grade Ⅰ-Ⅱ radiation gastroenteritis occurred in 9 patients, and grade Ⅰ elevated transaminase occurred in 3 patients. Conclusions: SFRT can effectively alleviate clinical symptoms and provide favorable local control in patients with advanced/recurrent metastatic large-volume malignant tumors, with manageable safety. Preliminary results suggest that SFRT can serve as a palliative treatment option for this patient population. The synergistic effect and long-term efficacy of sequential drug therapy (including immunotherapy) require validation with larger sample size or prospective studies.