Lamivudine is an antiretroviral (ARV) drug from category of nucleoside reverse transcriptase inhibitors (NRTI) for both the human immunodeficiency virus (HIV) and hepatitis B treatments. Besides, chitosan in nanoparticles is used as a matrix in good drug delivery systems for both hydrophobic and hydrophilic ARV drugs. Chitosan modification has been widely investigated to enhance its hydrophilicity properties to bind lamivudine. This study aims to modify chitosan nanoparticles (CSNP) using polyethylene glycol as a drug delivery system for lamivudine. CSNP was modified by polyethylene glycol, then loaded with lamivudine and crosslinked by sodium tri polyphosphate (TPP) to produce lamivudine nanodrug in a chitosan drug delivery system. According to the particle size analyzer (PSA), nanodrug has particle size approximately 79.25 nm. The encapsulation efficiency of nanodrug is 86.96 % from 28.98 % loading concentration. The drug release tests of lamivudine in phosphate buffer at pH of 3.0 for 4 h; pH of 6.8 and 7.4 for 24 h were 72.37; 84.96 and 80.40 % respectively.