Compared with previous studies focused on the effect of CNTs or antibiotics on aquatic organisms, our efforts were mainly devoted to the combined effect of CNTs and antibiotics on cyanobacterium Synechocystis sp. PCC 6803 to reveal the influencing mechanism of CNTs on the toxicity of antibiotics. CNTs exhibited an additive effect with CAP but an antagonistic effect with TC. Moreover, this study provides direct evidence for the molecular mechanisms of proteomic perturbations in Synechocystis sp. exposed to CNTs and/or antibiotics. This study provides a new insight into the molecular mechanisms of combined toxicity of multiple pollutants to cyanobacterium.