Background/aim: This study aimed to investigate the efficacy of pegylated liposomal etoposide nanoparticles (NPs) against T-47D and MCF-7 breast cancer cell lines. Materials and methods: Pegylated liposomal etoposide NPs were prepared by reverse phase evaporation method. The size, size distribution, and zeta potential of the NPs was measured by a Zetasizer instrument. The cytotoxicity of NPs was inspected by methyl thiazol tetrazolium assay. The release pattern of the drug from the vesicles was studied by the dialysis method. Drug loading and encapsulation efficiency (EE) were also measured. Results: The mean size, size distribution, and zeta potential of pegylated liposomal etoposide NPs were 491 ± 15.5 nm, 0.504 ± 0.14, and -35.8 ± 2.5 mV, respectively. Drug loading and EE were 10.3 ± 1.6% and 99.1 ± 2.8%, respectively. The etoposide release in the formulation was estimated at about 3.48% after 48 h. The cytotoxicity effect of etoposide NPs on T-47D and MCF-7 cell lines of breast cancer showed higher antitumor activity as compared with those of the free drug. Conclusion: Liposome-based NPs may hold great potential as a drug delivery system.