Objective To study the effect of Numb gene on CXCR4 expression and proliferation and migration of bladder cancer. Methods Human bladder cancer cells were divided into 3 groups:experimental group(transfected with Numb-ORF plasmid),negative-control group( transfected with blank vector),and blank-control group(no DNA transfected in). The expressions of Numb and CXCR4 were detected by real-time PCR and Western blotting respectively. Cell proliferation and migration were measured by MTS and Transwell assay respectively. Results Numb expressions in experimental group,negative-control group and blank-control group were 31. 044 ± 3. 350,4. 401 ± 0. 567 and 4. 287 ± 0. 341 respectively,with a statistical significance (F = 183. 418,P = 0. 000). CXCR4 levels in experimental group,negative-control group and blank-control group were 0. 344 ± 0. 167,0. 996 ± 0. 148 and 1. 010 ± 0. 106 respectively,with a statistical significance (F = 21. 355,P = 0. 002). In MTS assay,the absorb values in experimental group,negative-control group and blank-control group were 0. 615 ± 0. 057,0. 987 ± 0. 063 and 0. 957 ± 0. 066,with a statistical difference(F =33. 210,P = 0. 001). In Transwell assay,the numbers of migratory cells in experimental group,negative-con-trol group and blank-control group were 164. 667 ± 19. 858,670. 133 ± 38. 760 and 667. 533 ± 27. 610,with a statistical significance(F = 286. 788,P = 0. 000). Conclusion Overexpression of Numb can suppress the ability of proliferation and migration of the BIU-87 cells through down-regulation of CXCR4 expression in human bladder cancer.