Abstract: Celastrol (CEL) - chitosan oligosaccharide (CSO) loaded triptolide (TP) nanoparticles (Cel-CSO@TP NPs) were prepared, and their anticancer activity in vitro and in vivo was evaluated in this work． Cel-CSO@TP NPs were prepared by weak electrostatic forces． The morphology, particle size, Zeta potential, stability, entrapment efficiency, drug loading and in vitro release were characterized． The anti-pancreatic cancer activity was evaluated with CCK-8 cell viability test in vitro and anti-tumor test in vivo． Cel-CSO@TP NPs were found to be spherical nanoparticles with regular morphology with an average diameter of (177.87 ± 2.20) nm, a mean Zeta potential of (−36.51 ± 2.66) mV． The encapsulation efficiency and the drug loading were (64 ± 0.91)% and (16 ± 1.33)%, respectively．Drug release studies revealed that Cel-CSO@TP NPs had the effect of delaying drug release．Cel-CSO@TP NPs had better anti-tumor effects and lower toxicity than TP．Cel-CSO@TP NPs had stronger anti-pancreatic cancer activity than TP．