Abstract: Liposomes have been widely exploited in clinics. After entry into blood stream, liposomes absorb a large number of plasma proteins to form protein corona, which severely regulates in vivo performance of liposomes. It is of high importance to study the relationships among liposome surface properties, plasma protein components and liposome in vivo performance for clinical translation. In this review, we will summarize the factors affecting liposome protein corona, the effects of protein corona on liposome performance and the rational design of liposomes, aiming to accelerate clinical translation of liposome-based therapeutics.