Background: Zanubrutinib, a second-generation non-covalent Bruton's Tyrosine Kinase inhibitor (BTKi), with better BTK specificity, and fewer off-target effects. Zanubrutinib has demonstrated the confirmed effectiveness and safety in clinical trials such as SEQUOIA and ALPINE in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), and earlier studies showed its efficacy and safety profile of zanubrutinib monotherapy in the real world. Meanwhile, more valuable insights hope to be gained on zanubrutinib treatment in Chinese CLL/SLL patients (pts) outside of the clinical trial setting. This report provides some outcomes evaluated in a real-world study. Aims: This study further evaluated the effectiveness and safety of zanubrutinib monotherapy/combination treatment in Chinese CLL/SLL pts in a real-world setting. Methods: CLL/SLL pts who received zanubrutinib monotherapy/combination treatment for at least 3 months from Aug. 2017 to Jul. 2023 were enrolled from Jiangsu Province Hospital. The primary outcome was progression free survival (PFS). Baseline characteristics were also collated. Results: 77 pts were analyzed in all. Zanubrutinib was administered orally at 160 mg, twice daily (BID), mono or combined. Among the monotherapy pts, 20 (35.1%) pts were treatment naïve (TN) and 37 (64.9%) pts were refractory/relapsed (R/R). Among the combination treatment pts, 14 (70.0%) pts were TN and 6 (30.0%) pts were R/R. Baseline characteristics were shown in Table 1. The median follow-up time was 31.8 months, and the median PFS was not reached in the entire cohort. The 12-month PFS rate was 95.8% (95%CI 91.3-100.0%) while the 24-month PFS rate was 90.9% (95%CI 84.2-98.2%) (Figure A). After stratified by line of therapy in monotherapy, the estimated 12-month PFS rates of TN and R/R zanubrutinib monotherapy pts were 100.0% (95%CI 100.0-100.0%) and 91.3% (95%CI 82.3-100.0%) (Figure B). The estimated 24-month PFS rates of TN and R/R zanubrutinib monotherapy pts were 93.8% (95%CI 82.6-100.0%) and 84.9% (95%CI 73.5-98.1%). 4 (5.2%) pts interrupted treatment due to AE. 2 pts were TN and 2 pts were R/R. 2 pts received zanubrutinib monotherapy and 2 pts received combination treatment. The AEs included hemoptysis (1, 1.3%), platelet hemoglobin reduction and atrial fibrillation (1, 1.3%), bleeding points in both lower limbs (1, 1.3%), rash and edema (1, 1.3%). All treatment-interrupted pts still received zanubrutinib after interruption by the latest follow-up. 17 (22.1%) pts experienced treatment discontinuation due to progressive disease (PD) or transformation. No pts discontinued zanubrutinib treatment due to AE. PD was the most common reason for treatment discontinuation. 13 (16.9%) pts experienced PD and 4 (5.2%) pts experienced transformations. S ummary/Conclusion: Zanubrutinib shows good efficacy in Chinese CLL/SLL pts in the real-world study. Incidence of AE was low, and no treatment discontinued due to AE, revealing a good safety of zanubrutinib. PD was the main reason for treatment discontinuation. Therefore, the effectiveness and safety of zanubrutinib have been validated in the real world, consistent with clinical trials.