RNA-based therapeutics (e.g., mRNAs, siRNAs, microRNAs, ASOs, and saRNAs) have considerable potential for tumor treatment. The development and optimization of RNA modifications and delivery systems enable the stable and efficient delivery of RNA cargosin vivoto elicit an antitumor response. Targeted RNA-based therapeutics with multiple specificities and high efficacies are now available. In this review, we discuss progress in RNA-based antitumor therapeutics, including mRNAs, siRNAs, miRNAs, ASOs, saRNAs, RNA aptamers, and CRISPR-based gene editing. We focus on the immunogenicity, stability, translation efficiency, and delivery of RNA drugs, and summarize their optimization and the development of delivery systems. In addition, we describe the mechanisms by which RNA-based therapeutics induce antitumor responses. Furthermore, we review the merits and limitations of RNA cargos and their therapeutic potential for cancers.