Objective To evaluate the clinical value of obinutuzumab-based combination regimens in treating B-cell non-Hodgkin lymphoma (B-NHL), and to provide evidence for rational clinical drug use.Methods Following the Guidelines for Comprehensive Clinical Evaluation of Drugs (Trial Version 2021), a rapid health technology assessment was conducted. Data from drug instructions, the National Medical Products Administration, and other professional platforms were systematically integrated, as well as relevant literature and economic evaluation evidence of obinutuzumab-based combination regimens in the treatment of B-NHL. The comprehensive evaluation was conducted from six dimensions of safety, effectiveness, economy, innovation, suitability and accessibility.Results In terms of effectiveness, compared with rituximab-based regimen, obinutuzumab-based regimen significantly prolonged the progression-free survival (PFS) in newly diagnosed or relapsed/refractory B-NHL patients, though no significant difference in overall survival (OS) was observed. In terms of safety, the obinutuzumab-based regimen exhibited higher incidences of overall adverse events (AEs), grade ≥3 AEs, infusion-related reactions, neutropenia and thrombocytopenia than the rituximab-based regimen. Pharmacoeconomically, obinutuzumab-based regimens showed economic advantages across countries despite variations in willingness-to-pay thresholds. In terms of innovation, obinutuzumab is the first Fc-glycosylation modified humanized type Ⅱ anti-CD20 monoclonal antibody globally approved. Its suitability was enhanced by fixed-dose administration without body surface area (BSA)-adjusted dosing. In accessibility, obinutuzumab has been included in China's National Medical Insurance Negotiated Drug List, demonstrating high regional and market coverage with improved affordability and availability. Conclusion Obinutuzumab-based regimen outperform rituximab-based regimen in efficacy and cost-effectiveness in the treatment of newly diagnosed or relapsed/refractory B-NHL, albeit with higher AE rates. As the first-in-class humanized type Ⅱ anti-CD20 monoclonal antibody, obinutuzumab exhibits superior innovation, suitability, and accessibility.