Aim: PRMT5 and c-Myc were considered as oncogene of bladder cancer. Nevertheless, whether the interaction between of PRMT5 and c-Myc affect bladder cancer progress is unknown. Herein, we explore the above points and discuss deeply its' potential mechanism., Method: 5637 and T24 cells were study subjects in vitro. Western blot was used to examined the protein expression. CCK8 and transwell assay were used to analyze proliferation and invasion ability. Additionally, xenograft tumor model was established. Mice imaging experiment, Immunochemistry assay and western blot were carried out., Result: Western blot result showed successful transfection of PRMT5-siRNA and c-Myc-siRNA. PRMT5-siRNA could inhibit c-Myc expression, and decrease the proliferation and invasion of bladder cells. And c-Myc overexpression could reverse inhibitory action caused by PRMT5 silence. And in vitro studies found low-expression of c-Myc reduced proliferation and invasion of tumor cells and make the NF-κB pathway inactivation. In vivo studies also demonstrated that inhibiting PRMT5 could downregulate c-Myc expression and inhibit the bladder cancer progress, and the potential mechanism was likely to be related to NF-κB signaling pathway., Conclusion: In a word, low-expression of PRMT5 suppressed c-Myc, and thus inhibited proliferation and invasion ability of 5637 and T24 cells through NF-κB pathway., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)