Antiretroviral therapy remains the most effective means of managing the human immune deficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Application of therapeutics has been hampered by factors including poor bioavailability of most anti-retroviral compounds (ARV), side effects and an alarming emergence of drug resistant strains of the virus. Recent developments and use of drug delivery systems (DDS) has shown potential for improving the pharmacological profile of ARV. Amongst these complex DDS, liposomes have been explored for delivery of ARV. In this study, we have aimed at exploring efficient encapsulation of efavirenz (EFV), a potent ARV using different mass ratios of crude soybean lecithin and cholesterol. The EFV-loaded liposomes (EFL) were prepared using thin film hydration and evaluated for particle size, zeta potential (ZP), encapsulation efficiency (EE%), morphology and drug release studies. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), energy dispersity spectroscopy (EDS) and Fourier transform infrared (FTIR) spectroscopy were used for comprehensive physicochemical characterization of EFL. EFL exhibited high encapsulation (99%) in 1:1 crude lecithin to cholesterol mass ratio. The average particle size and Zeta Potential of EFL were found to be 411.10 ± 7.40 nm and − 53.5.3 ± 0.06 mV, respectively. EFL showed a relatively controlled EFV release behaviour that was similar to the dissolution profile of un-encapsulated EFV. This suggests that EFL represents a promising vehicle for effective EFV delivery while providing the advantages of a nano-scaled delivery system.