Background: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used to treat patients with diffuse large B-cell lymphoma (DLBCL) under National Health Insurance (NHI) scheme in Indonesia. This study aims to estimate its cost-effectiveness and budget impact. Methods: We conducted a cost utility analysis using Markov model over a lifetime horizon, from a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital data. Direct non-medical costs, indirect costs, and utility data were primarily gathered by interviewing the patients. We applied 3% discount rate for both costs and effect. All monetary data are converted into USD (1 USD = IDR 14,000, 2019). Probabilistic sensitivity analysis was performed. In addition, from a payer perspective, budget impact analysis was estimated using price reduction scenarios. Results: The incremental cost-effectiveness ratio (ICER) of R-CHOP was USD 4674/LYG and 9280/QALY. If we refer to the threshold three times the GDP per capita (USD 11,538), R-CHOP could thus be determined as a cost-effective therapy. Its significant health benefit has contributed to the considerable ICER result. Although the R-CHOP has been considered a cost-effective intervention, the financial consequence of R-CHOP if remain in benefit package under National Health Insurance (NHI) system in Indonesia is considerably substantial, approximately USD 35.00 million with 75% price reduction scenario. Conclusions: As a favorable treatment for DLBCL, R-CHOP ensures value for money in Indonesia. Budget impact analysis provides results which can be used as further consideration for decision-makers in matters related to benefit packages. © 2022, The Author(s).