As one of the gaseous signals in living cells, carbon monoxide (CO) not only participates in many biological activities but also serves as a therapeutic agent for the treatment of diseases. However, the limited applicability of CO in gas therapy emerges from the inconvenience of direct administration of CO. Here we reported the construction of guanidinylated CO-releasing micelles, which are composed of poly(trimethylene carbonate) (PTMC)-based CO donors. The in vitro studies demonstrated that micelles in the presence of light irradiation can induce cancer death, whereas no obvious toxicity to normal cells was observed. Moreover, the functionalization of guanidine groups imparts improved cellular uptake efficiency to micelles owing to the specific interactions with the surface of cells, which synergistically increase the anticancer capacity of the system. The guanidine-functionalized CO-releasing micelles provide a new strategy for the construction of CO-releasing nanocarriers, which are expected to find applications in gas therapeutics.