Objective To investigate the effect of anterior gradient 2 (AGR2) on the migration and invasion of nasopharyngeal carcinoma (NPC) cells by regulating the transforming growth factor-β (TGF-β)/SMAD signaling pathway. Methods Human normal nasopharyngeal epithelial cells (NP69) and NPC cells (5-8F, 6-10B, CNE-1) were cultured in vitro, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of AGR2 mRNA in the cells. The 5-8F cells were randomly assigned into control group, sh-NC group, sh-AGR2 group, and sh-AGR2+SRI-011381 group (sh-AGR2+TGF-β signaling pathway activator SRI-011381). qRT-PCR and Western blot were applied to detect the transfection efficiency of AGR2. Cell proliferation was measured by CCK8 assay and colony formation assay. Cell migration was measured by scratch test. Transwell assay was used to measure cell invasion. Cell apoptosis was determined by flow cytometry. The protein expressions of PCNA, MMP-2, MMP-9, TGF-β1 and p-SMAD2/SMAD2 were detected by Western blot. Results Compared with NP69 cells, the AGR2 mRNA expression was elevated in NPC cells. Compared with the control group or sh-NC group, the OD450, clone number, scratch healing rate, invasion number, expression levels of PCNA, MMP-2, MMP-9, TGF-β1, and p-SMAD2/SMAD2 in the sh-AGR2 group decreased, and the apoptosis rate was increased (P<0.05). Compared with the sh-AGR2 group, the OD450, clone number, scratch healing rate, invasion number, expression levels of PCNA, MMP-2, MMP-9, TGF-β1, and p-SMAD2/SMAD2 in the sh-AGR2+SRI-011381 group increased, and the apoptosis rate was decreased (P<0.05). Conclusion The expression level of AGR2 is elevated in NPC cells, which in turn promotes the proliferation, migration and invasion abilities of NPC cells and inhibits cell apoptosis. This may be achieved by regulating the TGF-β/SMAD signaling pathway.