Objective：This study aims to elucidate the role and molecular mechanism of JWA in regulating cell energy metabolism and inhibiting the migration of pancreatic cancer cells. Methods：Human pancreatic cancer Panc1 and Bxpc3 cells were treated with the JWA small molecule agonist JAC4. The assays of wound healing and transwell were used to determine cell migration；the mitochondrial energy metabolisms of cells were measured by Seahorse XF energy metabolism analyzer. The pancreatic cancer cells Panc1 were used to establish series vivo metastatic mice models. Western blotting was performed to determine the levels of protein expression in related molecules. Results：The mRNA expressions of JWA was significantly lower in pancreatic cancer tumor tissues and pancreatic cancer cells compared with that in adjacent normal tissues and normal pancreatic cells；JAC4 inhibited migrations of pancreatic cancer Panc1 and Bxpc3 cells，and inhibited pancreatic cancer metastasis in mice and reduces serum LDH levels. The mechanistic evidences indicated that JAC4 positively regulates FOXO3a through AMPK signaling pathway led to the activation of mitochondrial complex Ⅲ（UQCRC2），and enhanced the oxidative phosphorylation；at the same time，JAC4 suppressed glycolysis of pancreatic cancer cells. Conclusion：The inhibiting role of JAC4 on pancreatic cancer cells was realized by mitochondria metabolic reprogramming through the JWA/AMPK/FOXO3a/UQCRC2/FAK signaling.