The QS machinery of Pseudomonas aeruginosa, an opportunistic human pathogen, consists of three acyl-homoserine lactone (acyl-HSL) signaling systems, LasR-I, RhlR-I, and QscR. QscR, known as an orphan receptor and a repressor of other QS systems, operates its own regulon using N-3-oxododecanoyl HSL (3OC12), which is synthesized by LasI, as its signal. In this study, we addressed the role of QscR in interspecies communication. We found that QscR auto-activates its own transcription in the presence of 3OC12. In a single population of P. aeruginosa, where 3OC12 is the sole signal available for QscR, the QscR regulon is activated by 3OC12 produced by the LasI-R system. However, the broad signal specificity of QscR allowed it to respond to a non-P. aeruginosa signal, such as N-decanoyl HSL (C10) and N-3-hydroxydecanoyl HSL (3OHC10), which preferentially activated QscR to LasR. The signal extracts from Pseudomonas fluorescens and Burkholeria vietnamiensis also preferentially activated QscR. These non-P. aeruginosa signals activated QscR more strongly than 3OC12, the authentic P. aeruginosa signal. Since a variety of acyl-HSLs are produced in the multi-species habitat of nature, our study provides a clue for the particular situation that allows QscR to secede from the conventional QS cascade in mixed microbial community.