Background Follicular lymphoma (FL) is the second most common B cell lymphoma subtype and chemoimmunotherapy treatment is the standard therapy for patients with high tumor burden. Bulky disease was associated with shorter median PFS compared to non-bulky disease in FL patients. Radiation and anti-programmed death-1 (PD-1) monoclonal antibody are both effective in FL and also have a synergistic effect. We assessed the potential benefit of Tiselizumab (a humanized monoclonal antibody targeting PD-1), radiotherapy combined with RCHOP as first-line treatment in FL patients with bulky disease. Methods This was a single center, single arm, phase II study. Patients with previously untreated follicular lymphoma were enrolled from the department of lymphoma, Tianjin Medical University Cancer Institute and Hospital. The bulky disease was received radiation (dose:18~24Gy) before RCHOP. Patients began chemoimmunotherapy 1~2 weeks later than radiation. Treatment included Tiselizumab (200 mg iv d1) plus R-CHOP (rituximab 375 mg/m 2 intravenous [IV] day 2, cyclophosphamide 750 mg/m 2 IV day 3, doxorubicin 50 mg/m 2 IV day 3, vincristine 1.4 mg/m 2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21~28 days for one cycle ) for six cycles. Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response(CMR/PMR)after first-line chemo until 2 years. Response was assessed by PET/CT scan after cycle 4 and cycle 6. The primary endpoint was complete response rate (CRR). R esults FromFebruary 2021 to June 2023, 6 patients were enrolled. 4 patients finished all 6 cycles treatment. 1 patient was dead because of COVID-19 who was PMR after 5 cycles treatment. The last one with CMR stopped chemotherapy because of COVID-19 and only received 4 cycles treatment. The median follow-up is 15 months. 5 patients achieved CMR in the mid-term evaluation and were still on remission in June 2023. The CRR was 83.3% and the overall response rate was 100%. The common adverse events were nausea, vomiting, bloating, loss of appetite, constipation, and diarrhea. The most common grade 3/4 adverse events were neutropenia (66.7% ), thrombocytopenia (16.7% ), and leukopenia (66.7% ). Conclusion Tiselizumab, radiotherapy combined with RCHOP is effective and tolerable in the untreated FL patients with bulky disease. More patients will be enrolled to estimate the efficacy and safety.