Pseudomonas aeruginosa and Candida albicans can coexist in human body. There is a complex interaction between the two opportunistic pathogens which was defined as cross-kingdom interaction: Pseudomonas aeruginosa inhibits the morphological change of Candida albicans, the formation of bacterial biofilm and kill the hypha, and Candida albicans inhibits the formation of pyocyanine of Pseudomonas aeruginosa and the swarming motility. Cross-kingdom interaction may exist three mechanisms: quorum sensing, biofilm and toxicity. By secretion of signaling molecule N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), Pseudomonas aeruginosa inhibits conversion of Candida albicans from yeast to hypha. By secretion of signaling molecule farnesol, Candida albicans inhibits the formation of pyocyanie and swarming motility. It suggests that the cross-kingdom interaction is partly mediated by signal molecules. Due to the presence of cross-kingdom interaction, the pathogenicity of Pseudomonas aeruginosa and Candida albicans is impacted, helpful in choosing the better treatment.