Objective: The purpose of this study is to investigate the clinical and biological characteristics of chronic lymphocytic leukemia (CLL) patients with exportin 1 (XPO1) gene mutations, and to provide clues for clinical diagnosis and treatment. Methods: The clinical data of CLL patients with XPO1 mutations detected in the Department of Hematology of Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University) from March 2017 to March 2022 were retrospectively analyzed. The clinical data, treatment response and survival outcomes of the treatment native (TN) and relapsed/refractory (R/R) patients with XPO1 mutation were compared. Results: 15 patients(2.8%) with XPO1 mutations were included in the total population of 543 CLL patients, 9 in the TN group and 6 in the R/R group. And the hot spot mutation was E571K. Most of the patients were Rai III-IV stage, Binet B-C group, and unmutated IGHV status. XPO1 mutation could co-occur with NOTCH1 mutation，SF3B1 mutation，and ATM mutation，regardless of disease state. While TP53 and XPO1 mutations co-occurrence tend to be observed in the R/R group (TN: 11.1%; R/R: 50%). The median time to first treatment (TTFT) for patients with XPO1 mutations was 5.2 (0-87.4) months, the median progression-free survival (PFS) was 30.3 (22.4-45.9) months, and the median overall survival (OS) was 102.4 (4.3-152.5) months. In the XPO1 wild-type group, median TFS, PFS and OS were 8.1 (0-162.3) months, 32.5 (2-152.1) months, and 49.8 (0.4-284.4) months, respectively. Conclusion: Our data suggest a lower incidence of XPO1 mutations in CLL. It seems to co-occur frequently with other gene mutations. Relapsed/refractory patients have more XPO1 mutations and higher tumor burden than treatment native patients . TTFT and PFS of CLL patients with XPO1 mutations tend to be shorter than those of XPO1 wild-type cases.