Objective To modify polyargine (PLR) with polyethylene glycol (PEG) and to observe the effect of PEG modification on PLR cytotoxicity and efficiency of PLR-mediated RNA interference. Methods ¹HNMR was used to characterize PLR-PEG and gel electrophoresis was adopted to determine the siRNA-packing capacity of PLR-PEG. The cytotoxicity of PLR-PEG, cellular uptake and RNA interference efficiency of PLR-PEG/siRNA complexes were investigated using prostate cancer stem-like cells(RC-92a/hTERT). Results ¹HNMR results showed the successful synthesis of PLR-PEG.It was found that PEG modification decreased cytotoxicity of PLR and reduced cellular uptake of PLR/siRNA complexes, but the reduction of cellular uptake was limited when N/P was high. The modification also inhibited the efficiency of PLR-mediated RNA interference, but the influence of PEG modification was not notable within a certain range. Conclusion PEG -modified PLR may be a promising vector for gene therapy targeting prostate cancer stem cells.