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RNA interference (RNAi) therapy has emerged as a promising cancer therapy platform; however, there is an ongoing need for a safe and effective delivery carrier for siRNA. The present study demonstrates for the first time the systemic in vivo delivery of nanosized complexes of quaternized starch (Q-starch) and siRNA to effectively target cancer in a murine model. Our results show that Qstarch/siRNA composite nanoparticle complexes are safe for systemic administration, with no evident toxicities. Encouragingly, the results demonstrate their cellular uptake in the tumor and 63% gene silencing post intratumor injection. Moreover, a biodistribution study reveals favorable accumulation of the composite nanoparticles in the tumor site post systemic administration. The gene-silencing results are encouraging, although not sufficient for therapeutic application, and raise the need to further investigate the potential of Q-starch/siRNA complexes in terms of genesilencing efficiency and of tumor targeting and stability following systemic administration. Overall, our composite nanoparticles show promising potential for RNAi delivery to tumor sites, with their accumulation in the lungs suggesting that there may be particular merit in investigating the use of Q-starch/siRNA complexes to treat lung cancer.