The invention discloses a star-shaped polymer containing a lipoyl group at the end, a preparation method thereof, polymer nanoparticles prepared therefrom and applications thereof. The star-shaped polymer containing lipoyl group in the side chain is obtained by esterification. The degree of LA substitution is controllable and has excellent biocompatibility. It can be used to control the drug release system, and the prepared cancer-targeted reduction-sensitive reversible cross-linked polymer Nano-particles and nano-drugs support stable long-term circulation in the body, but are highly enriched in cancer tissues and efficiently enter cells, quickly de-crosslink and release drugs in cells, efficiently and specifically kill cancer cells, and effectively inhibit the growth of cancer without causing toxic side effects.