Quorum sensing inhibitors (QSIs) have attracted increasing attention due to their potential roles as the antibiotic alternatives. The combination of QSIs and antibiotics in clinical use and their subsequent release into the environment may result in joint effects on the ecology and environment, which has not received enough concerns yet. In this study, eight potential QSIs and three types of commonly used antibiotics, i.e., sulfonamides (SAs), beta-lactams and tetracyclines (TCs), were investigated for their combined toxicity on Escherichia coli (E.coli). The QSAR models for the combined toxicity were constructed using the interaction energies between the chemicals and their target proteins as calculated by molecular docking. It was revealed that the SAs and QSIs presented either additive or antagonistic joint effects in the mixture toxicity test, while beta-lactams and TCs showed only antagonistic effects with the QSIs. The analysis on the coefficients in the QSAR models suggested that the QSIs in the mixtures were more involved in the interaction with the proteins than the antibiotics. This study will help better understand the risks of joint exposure to the antibiotics and QSIs, and provide a new perspective for the study of the combined toxicity mechanism. (C) 2017 Elsevier B.V. All rights reserved.