Etravirine is an antiviral belonging to biopharmaceutics classification system class IV due to low aqueous solubility and poor permeability. In this study, to augment the dissolution profile of etravirine, solid lipid nanoparticles have been formulated by utilizing lipid mixture of Compritol® 888 ATO and Gelucire® 50/13 as lipids and poloxamer 188 as surfactant by hot homogenization technique. Effect of variables, ratio of lipids, the concentration of surfactant and sonication time on responses like: Percentage yield, percentage encapsulation efficiency and percentage drug release were studied at 2 different levels and were statistically analyzed using 23 full factorial statistical design. The effect of factors on responses was well explained by a significant linear model. The optimized solid lipid nanoparticles preparation was evaluated for zeta potential, size of the particle and polydispersity index. The solid lipid nanoparticles displayed a zeta potential of 36.2 mV, the particle size of 178 nm and polydispersity index value of 0.075 indicating the solid lipid nanoparticles were nano sized and monodispersed. The absence of interaction of drug with excipients was confirmed with differential scanning calorimetry and X-ray powder diffractometer. In vitro drug profile of optimized solid lipid nanoparticles formulation was found to be 43.68 % in comparison with pure drug (19.99 %) and the release kinetics for optimum preparation was explained by first-order kinetics. Based on promising in vitro results it can be concluded that solid lipid nanoparticles of etravirine can be formulated based on validated factorial design, which may be a potential drug delivery system in the management of human immunodeficiency virus infection.