Background and Aims Pancreatic cancer is a digestive system tumor with high degree of malignancy. Early metastasis is the main cause for death of pancreatic cancer patients. Sinomenine is an alkaloid extracted from the dried cane of rattan, which has the pharmacological effects such as analgesic, anti-inflammatory and immunosuppressive properties. Studies have found that the NF-κB signaling pathway is closely related to the metastasis of pancreatic cancer, and sinomenine can inhibit the activation of the NF-κB signaling pathway. Therefore, this study was designated to investigate the inhibitory effect of sinomenine on the migration and invasion of pancreatic cancer cells and its association with the NF-κB signaling pathway.Methods The pancreatic cancer Capan-1 cells were treated with different concentrations of sinomenine (400, 800, and 1 600 mg/L), with untreated Capan-1 cells as control, and then, the changes in migration and invasion abilities were detected by scratch healing assay and Transwell assay, and the expressions of NF-κB protein as well as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were determined by Western blot. After that, the influences of the NF-κB signaling pathway agonist TNF-α (20 mg/L) on the actions exerted by sinomenine (1 600 mg/L) were observed.Results In Capan-1 cells after treatment with each concentration of sinomenine compared with control Capan-1 cells, the migration and invasion abilities were all decreased, and the nuclear translocation of NF-κB pancreatic cancer was subdued (cytoplasmic NF-κB increased and nuclear NF-κB decreased), and the expressions of ICAM-1 and VCAM-1 were down-regulated, all of which presented a certain concentration-dependent pattern (P<0.05 or P<0.01). The effects exerted by TNF-α were totally opposite to those of sinomenine on Capan-1 cells, and the effects of inhibiting migration and invasion as well as down-regulating adhesion molecule expressions exerted by sinomenine on Capan-1 cells were partially reversed by simultaneous addition of TNF-α (P<0.05 or P<0.01).Conclusion Sinomenine can inhibit the migration and invasion of pancreatic cancer cells, and the mechanism may be associated with its suppressing the activation of NF-κB signaling pathway, and thereby down-regulating the expressions of downstream adhesion molecules. Sinomenine is probably a potential therapeutic drug for pancreatic cancer.