Nanoparticles　based　on　Radix　pseudostellariae　protein-polysaccharide　conjugates　were　self-assembled　via　pH　adjustment　and　thermal　treatment.　The　fabricated　nanoparticles　(CP3)　were　spherical　with　narrow　size　distribution　of　125.0　nm　in　diameter.　The　doxorubicin　(DOX)　-loaded　CP3　nanoparticles　exhibited　pH-sensitive　release　behavior　and　accelerated　the　release　of　DOX　under　the　acidic　pH　simulating　tumor　microenvironment　and　endosomal　pH.　In　HepG2　uptake　studies,　CP3-DOX　nanoparticles　notably　improved　the　internalization　of　DOX,　which　was　1.56-fold　compared　with　free　DOX.　CP3-DOX　nanoparticles　could　serve　as　P-glycoprotein　efflux　pump　inhibitor　and　be　internalized　into　HepG2　cells　via　clathrin-dependent　endocytosis.　Moreover,　the　cytotoxicity　effect　of　DOX　on　HepG2　cells　was　elevated　after　the　encapsulation　by　CP3,　with　a　lower　IC50　value　of　0.25　μg/mL.　The　findings　suggested　that　the　pH-sensitive　CP3-DOX　nanoparticles　has　a　great　potential　in　facilitating　the　efficacy　of　DOX　in　cancer　cells,　and　the　obtained　CP3　could　be　a　good　candidate　as　nanocarrier　for　the　encapsulation　and　delivery　of　functional　compounds.　©　2019　Elsevier　Ltd