In this study, the effect of protonectin as an antimicrobial peptide in its encapsulated form into PEG-PCL Nano micelle on bioability of human cancer lung of A549 was investigated. By applying 12 µg/ml and 50 µg/ml of the peptide in its encapsulated form and post 24 h and 48 h cell treatment, highest cytotoxicity on A549 was noticed. Biodegradable and biocompatible micelles were made by connecting poly (ethylene glycol) and poly (Ɛ-caprolactone) (PEG-PCL). NMR and FT-IR techniques were applied to characterize PEG-PCL micelle, while the properties of encapsulated peptide into PEG-PCL were further researched by using HPLC, scanning electron microscope (SEM), dynamic light scattering (DLS) as well as zeta potential. The impacts of PEG-PCL encapsulated protonectin with yield loading of 89.7% on the gene expression pattern of metastatic factors BMI-1 and CD44 were examined by the real-time RT PCR. Outcomes exhibited that BMI1 gene expression was down-regulated at a higher level compared to that of CD44 at the concentration of 12 µg/ml, and post 24 and 48 h. In conclusion, our finding supports a novel drug delivery system that can be applicable to enhance the solubility of insoluble drugs, has harmless effects on cancer cells on its own, and is cytotoxic in its encapsulated form.