The invention discloses a reversible cross-linked biodegradable polymer vesicle with an asymmetric membrane structure, a preparation method thereof and an application in nucleic acid medicine. Synthesized triblock polymer PEG-P(TMC-DTC)-PEI, PEG-P(DLLA-DTC)-PEI self-assembled and self-crosslinked to obtain polymersomes with asymmetric membrane structure, or connected with Targeted RCCPs are self-assembled by targeting molecules, the inner shell is PEI for complexing and loading nucleic acids through electrostatic interaction; the membrane is reversibly cross-linked biodegradable and biocompatible polyester / polycarbonate, side chain The dithiolane is similar to the human body's natural antioxidant lipoic acid, and the outer shell is based on PEG, which can target cancer cells. To study carrier complex functional siRNA, its in vivo and in vitro gene silencing effects, in vivo blood circulation and biodistribution, treatment of mice bearing orthotopic lung cancer and toxic and side effects, it is expected to become a simple, stable, multifunctional nano System platform for efficient, active targeted delivery of siRNA to tumors in situ.