The success of siRNA gene therapy requires the availability of safe and efficient delivery systems. In the present study, we investigated poly(vinyl benzyl trimethylammonium chloride) (PVTC) and its block copolymer with poly(oligo(ethyleneglycol) methacrylate) (POEGMA) as delivery vector for siRNA. Small polyplexes ranging from 8 to 25 nm in diameter were formed in aqueous solution by spontaneous self-assembly of both the homopolymer and block copolymer with siRNA and the formed particles were stable at physiological ionic strength. It was shown that when human ovarian adenocarcinoma cells were transfected, siRNA polyplexes based on PVTC (40 kDa) and PVTC-POEGMA-4 (PP4, 34 kDa) efficiently induced luciferase gene silencing to the same extent as the formulation based on a commercial lipid (Lipofectamine®) (˜80%), and showed higher gene silencing than the linear polyethylenimine formulation linear polyethylenimine (˜35%). Importantly, the POEGMA block polymers displayed a significantly lower cytotoxicity as compared to L-pEI. siRNA polyplexes based on the block polymers displayed high cellular uptake resulting in ˜50% silencing of luciferase expression also in the presence of serum. These results demonstrate that PVTC-based polymers are promising siRNA delivery vectors.