It is much importance to develop novel multifunctional delivery systems for the combination therapy of drug and gene. In this work, a novel conjugate, polyethylene glycol-polyethylenimine-tetrachloroplatinum (IV) (PEG-PEI-Pt), with good abilities of antitumor and gene delivery was proposed by combining PEG (Mw 3400 Da), low molecular weight PEI (Mw 800 Da), and tetrachloroplatinum (IV). The antitumoral and gene transfection activities of PEG-PEI-Pt were analyzed in many tumor (A549, A375, HepG-2, HuH-7, and B16 cells) and normal (COS-7 cells) cell lines. Similar to cisplatin (one platinum anticancer drug), PEG-PEI-Pt showed much higher sensitivity in tumor cells than in normal cells. More importantly, PEG-PEI-Pt had a potential to treat drug-resistant tumors. Almost no transfection efficiency was observed for PEI (Mw 800 Da) and PEG-PEI. Very interestingly, PEG-PEI-Pt could condense plasmid DNA efficiently, and exhibited good transfection efficiency in B16, HepG-2, A375 and COS-7 cells, comparable to even higher than PEI 25 kDa. In addition, PEG-PEI-Pt could also effectively deliver siRNA into the cytoplasm of tumor cells. With the good antitumoral and gene delivery abilities, PEG-PEI-Pt may have a great potential for combination therapy of drug and gene. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 123: 1509-1517, 2012