Objective To investigate the effects of Ras?related protein Rab?2B （RAB2B） on the biological behaviors of pancreatic cancer cells and elucidate its underlying mechanism. Methods PANC?1 cells， which exhibit relatively high RAB2B expression， and BXPC?3 cells， which display relatively low RAB2B expression， were selected from five pancreatic cancer cell lines. RAB2B?siRNA and pcDNA3.1?RAB2B plasmids were transfected into PANC?1 and BXPC?3 cells using a cell transfection technique. The CCK?8 assay was employed to evaluate the proliferative capacity of pancreatic cancer cells following RAB2B intervention. Wound healing and Transwell chamber assays were utilized to assess the migratory and invasive capabilities of pancreatic cancer cells. Additionally， the mRNA and protein expression levels of RAB2B， NF?κB， and Fibronectin 1 （FN1） were analyzed by qRT?PCR and Western blot （WB）， respectively. Results RAB2B mRNA and protein expression levels were significantly downregulated in PANC?1 cells following transfection （P < 0.05）. CCK?8 assay results demonstrated that the proliferative capacity of PANC?1 cells was markedly reduced （P < 0.05）， and the wound?healing ability was substantially impaired （P < 0.01） upon RAB2B knockdown. Transwell assays revealed a significant decrease in cell migration （P < 0.01）， while Western blot analysis indicated that the expression levels of phosphorylated p65 and FN1 were notably diminished （P < 0.01）. Conversely， overexpression of RAB2B reversed these aforementioned alterations. Conclusions Knockdown of RAB2B in PANC?1 cells significantly suppresses cell proliferation and migration， whereas overexpression of RAB2B in BXPC?3 cells markedly promotes these processes. This effect is likely mediated through the activation of the NF?κB signaling pathway and the subsequent regulation of FN1 expression.