Abstract Messenger RNA (mRNA) has received great attention in the prevention and treatment of various diseases due to the success of coronavirus disease 2019 (COVID‐19) mRNA vaccines (Comirnaty and Spikevax). To meet the therapeutic purpose, it is required that mRNA must enter the target cells and express sufficient proteins. Therefore, the development of effective delivery systems is necessary and crucial. Lipid nanoparticle (LNP) represents a remarkable vehicle that has indeed accelerated mRNA applications in humans, as several mRNA‐based therapies have already been approved or are in clinical trials. In this review, the focus is on mRNA‐LNP‐mediated anticancer therapy. It summarizes the main development strategies of mRNA‐LNP formulations, discusses representative therapeutic approaches in cancer, and points out current challenges and possible future directions of this research field. It is hoped that these delivered messages can help further improve the application of mRNA‐LNP technology in cancer therapy.