Background: We aimed to compare the cost-effectiveness of bruton tyrosine kinase inhibors (BTKis) versus bendamustine-rituximab (R-bendamustine) as a first-line treatment for Chinese patients with relapsed or refractory chronic lymphocytic leukemia. Methods: A partitioned survival model was constructed using TreeAge Pro 2022 software and transition probabilities were estimated from the reported survival probabilities using parametric survival modeling. One-way analysis and probabilistic sensitivity analysis were performed to explore the uncertainty of the modeling results. In addition, several scenario analyses were evaluated. Results: In comparison to R-bendamustine, zanubrutinib had an incremental cost-effectiveness ratio (ICER; life years) and ICER (quality-adjusted life years) of US$12,173.38 and $17,983.40, respectively. While ibrutinib had a higher ICER relative to R-bendamustine. Conclusion: Zanubrutinib was cost-effective for patients with relapsed or refractory chronic lymphocytic leukemia in China.