The recent growing emergence of  H5N1 Avian influenza virus (AIV) mutants calls for the urgent need for new effective antiviral drugs against  AIV. Quercetin, is a promising natural candidate for treatment and prevention of AIV infection but  unfortunately, low solubility and poor bioavailability of quercetin hinders its use in the medical field. Nanotechnology offers an innovative solution for enhancing quercetin solubility and bioavailability and subsequently boosts its therapeutic effect. In the current study quercetin nanoparticles were prepared by nanoprecipitation technique, quercetin nanoparticles showed a particle size range from 182nm to 240nm at flow rate 10 ml/ min, solvent/antisolvent volume ratio 1:12, stirring speed 1300 rpm and drug concentration 5mg/ml. The determined safe dilution of quercetin nanoparticles 10µg/ml had a significant inhibitory effect on the avian influenza virus H5N1 strain (EPI573317) indicated by reduction of the virus titer and the CPE in MDCK cells. Quercetin nanoparticles could be used as a new promising inhibitor for H5N1 AIV and is expected to be on the top of candidates as antiviral against influenza virus in the near future.