Objective To evaluate the efficacy of combined ABZ and PZQ and their solid lipid nanoparticles in chemoprophylaxis of cystic echinococcosis (CE). Methods ABZ and PZQ loaded solid lipid nanoparticles (SLNs) were prepared by high shear homogenization and microemulsion congealing techniques with some minor modification. Nanoparticles average size, polydispersity index (PDI), and particle size distribution were determined by scanning electron microscopy (SEM) and photon correlation spectroscopy. Forty females BALB/c were experimentally infected by protoscoleces (PSC) and randomly divided into four equal groups of 10 mice. After the end of the 3 months treatment period and 2 months rest, mice were sacrificed and the peritoneal cavity was opened for removal, counting, measuring, and histological analysis of hydatid cyst. Results The results indicated that ABZ and PZQ chemoprophylaxis treatment reduced the wet weight and size of developed cysts 77.3% and 79%, respectively. The corresponding result for the ABZ and PZQ loaded SLNs was 83% and 85%, respectively. Conclusions This study for the first time demonstrated that ABZ and PZQ loaded SLNs is superior to free ABZ and PZQ for the chemoprophylaxis of CE in mice.