Abstract: The discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) has profoundly influenced the development of gene-editing technique and has also shown extraordinary potential in the treatment of various diseases. In recent years, non-viral delivery systems, especially smart stimuli-responsive non-viral delivery systems, have attracted more and more attention because of their advantages such as excellent biocompatibility, ease of physical or chemical modification, and ease of largescale production. The smart stimuli-responsive delivery systems can control the CRISPR-Cas9 genome editing by sensing and responding to specific endogenous or exogenous signals, making genome editing more efficient and precise while reducing the off-target effects. This review briefly introduces the latest progress of smart stimuli-responsive nanosystems for CRISPR-Cas9 delivery and discusses the current problems and future challenges.