Pseudomonas aeruginosa, the main conditional pathogen causing nosocomial infection, is a gram-negative bacterium with the largest genome among the known bacteria. The main reasons why Pseudomonas aeruginosa is prone to drug-resistant strains in clinic are: the drug-resistant genes in its genome and the drug resistance easily induced by single antibiotic treatment. With the development of high-throughput sequencing technology and bioinformatics, the functions of various small RNAs (sRNA) in Pseudomonas aeruginosa are being revealed. Different sRNAs regulate gene expression by binding to protein or mRNA to play an important role in the complex regulatory network. In this article, first, the importance and biological functions of different sRNAs in Pseudomonas aeruginosa are explored, and then the evidence and possibilities that sRNAs served as drug therapeutic targets are discussed, which may introduce new directions to develop novel disease treatment strategies.