〔Abstract〕 Objective To analyze the clinical significance of elevated CHMP2B expression in pancreatic cancer, and to explore the oncogenic mechanism of CHMP2B in pancreatic cancer. Methods A transcriptomic analysis conducted on the GEPIA website revealed CHMP2B expression in over 20 types of malignant tumors. The relationship between CHMP2B expression and disease-free survival and overall survival of pancreatic cancer was analyzed. The correlation between CHMP2B, MAP1LC3B and P62 expression was analyzed by TCGA database. The overexpression plasmid of CHMP2B factor was transfected with Lipofectamine 2000 in MIA PaCa-2 cells, and the overexpression of CHMP2B factor in MIA PaCa-2 was verified by Western blot. The effect of overexpression of CHMP2B on tumorigenic ability of MIA PaCa-2 cells was verified by clonal formation experiment. The effect of overexpression of CHMP2B on proliferation, migration and invasion of MIA PaCa-2 cells was verified by CCK-8 and Transwell experiments. The localization of CHMP2B factor was detected by immunofluorescence staining. The correlation between CHMP2B, MAP1LC3B and P62 expression was analyzed by TCGA database. The expression of MAP1LC3B and P62 in CHMP2B overexpression was verified by qPCR. Results The expression of CHMP2B factor increased in pancreatic cancer(P<0.01). Overexpression of CHMP2B factor was associated with overall survival and disease-free survival(P<0.01). The high expression of CHMP2B promoted the tumorigenesis of MIA PaCa-2 cells in pancreatic cancer, and also promoted the proliferation, migration and invasion of pancreatic cancer. Immunofluorescence staining showed that CHMP2B was distributed in both nucleus and cytoplasm and correlated with vesicle secretion. Moreover, CHMP2B was positively correlated with the expression of autophagy marker MAP1LC3B while inhibiting the expression of P62. Conclusion The high expression of CHMP2B in clinical pancreatic cancer tissue samples is consistent with the high expressionin vitropancreatic cancer cell lines. CHMP2B is localized in both nucleus and cytoplasm, involving in vesicle transport and lysosomal autophagy. In the pancreatic cancer cell line MIA PaCa-2, CHMP2B is positively correlated with the expression of autophagy marker MAP1LC3B and inhibits the expression of P62. It is concluded that CHMP2B is related to autophagy in promoting the malignant degree of pancreatic cancer. CHMP2B meets the high nutritional metabolic requirements of pancreatic cancer cells by regulating vesicular transport and autophagy, thus promoting the malignant biological behavior of pancreatic cancer.