Nanoparticles　(NPs)　can　be　used　to　design　for　nanomedicines　with　different　chemical　surface　properties　owing　to　their　size　advantages　and　the　capacity　of　specific　delivery　to　targeted　sites　in　organisms.　The　discovery　of　the　presence　of　protein　corona　(PC)　has　changed　our　classical　view　of　NPs,　stimulating　researchers　to　investigate　the　in　vivo　fate　of　NPs　as　they　enter　biological　systems.　Both　NPs　and　PC　have　their　specificity　but　complement　each　other,　so　they　should　be　considered　as　a　whole.　The　formation　and　characterization　of　NP-PC　complexes　provide　new　insights　into　the　design,　functionalization,　and　application　of　nanocarriers.　Based　on　progress　of　recent　researches,　we　reviewed　the　formation,　characterization,　and　composition　of　the　PC,　and　introduced　those　critical　factors　influencing　PC,　simultaneously　expound　the　effect　of　PC　on　the　biological　function　of　NPs.　Especially　we　put　forward　the　opportunities　and　challenges　when　NP-PC　as　a　novel　nano-drug　carrier　for　targeted　applications.　Furthermore,　we　discussed　the　pros　versus　cons　of　the　PC,　as　well　as　how　to　make　better　PC　in　the　future　application　of　NPs.