pH responsive maleylated lignin-g-polyvinylpyrrolidone (MEHL-g-PVP) nanoparticles with a diameter of about 50 nm were synthesized by free radical polymerization and self-assembly using enzymatic lignin (EHL) and N-vinylpyrrolidone (NVP) as raw materials. The effects of chemical modification, polymer concentration, water addition rate, stirring speed, initial water content and drug dosage on the morphology, size and drug-carrying properties of nanoparticles were investigated. The results showed that the maximum drug loading of nanoparticles could reach 35.1% and the encapsulation efficiency was 64.3%. In vitro drug release showed that MEHL-g-PVP had obvious pH response ability, and the release amount of ibuprofen (IBU) was 11.1% and 63.75% in 72h in simulated intestinal environment and gastric juice of human body, respectively. The results of in vitro cytotoxicity test showed that MEHL-g-PVP drug-loaded nanoparticles had no cytotoxicity to normal cells and had a good inhibitory effect on colon cancer cells. MEHL-g-PVP nanoparticles are expected to become an ideal carrier material for oral drugs.