Abstract: Objective To explore the differences in expression level of miR-181b (miR-181b) in CD19⁺ B lymphocytes in patients with chronic lymphocytic leukemia (CLL) and analyze its clinical significance. Methods Fifty patients with CLL, and collecting healthy controls 20 cases. All patients took 15ml of peripheral blood and the total RNA of CD19⁺ B lymphocyte was extracted after sorting with CD19 magnetic beads, and the expression lever of miR-181b was measured by TaqMan probe. The difference expression lever of miR-181b in prognostic groups were analyzed, such as clinical stages, Serological indicators, CD38, Zeta chain related protein kinase-70, immunoglobulin heavy chain variable region and Abnormal genetics. Survival analysis was performed on the above indexes. Results ① The expression lever of miR-181b in CD19⁺ B lymphocytes in Fifty patients with CLL was significantly lower than the healthy controls (P<0.01). ② The expression level of miR-181b in different groups:according to the prognosis of FISH groups, the poor prognosis group was significantly lower than the favorable prognosis group (P<0.05), ATM deletion group was significantly lower than the ATM normal group (P<0.05), There was no statistical difference in the expression level of miR-181b in other groups (P>0.05). ③ Survival analysis:The expression level of mir-181b was divided into low expression group and high expression group by median of 0.033. The comparison showed that the OS of mir-181b low expression group was shorter than the mir-181b high expression group (P<0.05). Combined COX multivariate analysis with poor prognostic factors, the results showed that the high-risk group of FISH prognosis group, P53 deletion, ATM deletion, miR181b lower expression were all independent prognostic factors affecting survival (P<0.05). Conclusion The expression level of mir-181b in CLL patients is significantly lower than normal people, and the low expression of mir-181b is an independent prognostic factor of CLL.