Objective: To construct a stable pancreatic cancer cell line with high expression of the G-protein signaling modulator 2 (GPSM2), for investigating the relationship between GPSM2 and migration ability of human pancreatic cancer cells. Methods: The plasmids over-expressing GPSM2 gene (pCMV-Tag 3B-GPSM2) were constructed and then were identified. Human pancreatic cancer MIA-PaCa-2 cells were transfected with pCMV-Tag 3B-GPSM2 (GPSM2 transfection group) or empty pCMV-Tag 3B vectors (negative control group), with untreated MIA-PaCa-2 cells as blank control. In each group of cells, the GPSM2 mRNA expressions were measured by RT-PCR, the protein expressions of GPSM2 and β-catenin were determined by Western blot analysis, and the migration abilities were tested by Transwell assay, respectively. Results: The recombinant cell line with stable high GPSM2 expression was successfully constructed. In GPSM2 transfection group compared with blank control group, the GPSM2 mRNA expression was significantly up-regulated, with a 73.3-fold up-regulation, the protein expression levels of GPSM2 and β-catenin were significantly elevated, and the number of migrated cells was significantly increased (all P<0.05). In addition, a positive linear relationship existed between GPSM2 and β-catenin expressions in pancreatic cancer cells (P<0.05). There was no statistical difference in any of the indexes between negative control group and blank control group (all P>0.01). Conclusion: Up-regulating GPSM2 expression in pancreatic cancer cells can increase the migration ability of pancreatic cancer cells, which may be associated with increased β-catenin protein expression.