Tenofovir alafenamide (TAF) is used as a hepatitis B virus (HBV) nucleotide reverse transcriptase inhibitor for the treatment of chronic HBV infection. However, the use of TAF suffers from its poor solubility and low bioavailability. Therefore, this study prepared and characterized chitosan nanoparticles (CHS NPs) loaded with TAF. Morphological findings demonstrated that CHS NPs are roughly spherical and homogeneous in shape. Besides, TAF‐loaded CHS NPs displayed the hydrodynamic diameter, zeta potential, and PDI of approximately 340 nm, 48.9 mV, and 0.65, respectively. The encapsulation efficiency is at about 50%, and TAF is released about 93% at the end of 80 hours at pH 7.4. In addition, human hepatocellular carcinoma cells (HepG2) are used for cell viability studies and it is observed that TAF‐loaded CHS NPs has 1.24 times less viable cells as compared to the control. Collectively, TAF‐loaded CHS NPs could be used as an efficient formulation for the treatment of chronic HBV infection.