Nanomaterial-based pancreatic cancer treatment has received widespread attention and rapid development in the past few years. The major challenges include the poor combination of diagnosis and therapy, the difficulty in targeting therapy from the root and the unsatisfactory antitumor efficiency, which is accompanied by a great risk of relapse and metastasis. In this work, a positively charged lipid bilayer membrane is coated on reduced graphene oxide@gold nanostar (rGO@AuNS) for photoacoustic/photothermal dual-modal imaging-guided gene/photothermal synergistic therapy of pancreatic cancer. In addition, the cross-linking of folic acid on the surface of rGO@AuNS-lipid can specifically bind after recognizing folic acid receptors on the surface of cancer cells, and greatly improve the targeting ability of the nanomaterial and the performance of imaging diagnosis by receptor-mediated endocytosis. Moreover, the photothermal and gene (targeting G12V mutant K-Ras gene) synergistic therapy shows outstanding anticancer efficacy for pancreatic cancer tumor bearing mice, and it is noteworthy that the treatment groups have anti-liver metastasis of pancreatic cancer.