Abstract: Cancer is considered as one of the major diseases endangering human health in the world, it is urgent to find a safer and more efficient treatment for cancer therapy. Gene therapy with ribonucleic acid (RNA) drugs could regulate the expression of tumor related genes, and exhibit good anti-tumor therapeutic potential in preclinical and clinical trials. Based on the differences between tumor tissues and normal tissues in microenvironment signal characteristics such as pH, specific enzyme concentration or redox gradient, various microenvironment responsive nanocarriers had been studied and developed to deliver RNA drugs to tumor tissues and cells, improving the anti-tumor efficacy of RNA drugs and reducing toxic and side effects. This paper reviews the pathophysiological characteristics of tumor microenvironment and various strategies of tumor microenvironment responsive nanocarriers, in order to provide reference for the design of safe and efficient RNA drug delivery system for cancer therapy.