Antibody-based sensors are the most widely used for screening antibiotic residues in food samples.However,these sensors always suffer from cross-reacting antibiotics which are able to bind the employed antibodies in a manner similar to the target,thus resulting in inaccurate quantification.In this study,we developed a highly specific and sensitive chemiluminescence aptasensor for sulfamethazine(SMZ)by employing the supernormal selectivity of a new selected aptamer.Four SMZ-specific aptamers(Kdranging from 79-274 nM)were selected in vitro by MB-SELEX with an intentional counter selection to avoid the recognition other sulfonamides,which is impossible to achieve in the corresponding procedure of antibody production.The binding mechanism of aptamers for SMZ was further analyzed and clarified with molecular simulation and docking(Discovery Studio 4.5(San Diego,CA,USA).Under optimum conditions,the chemiluminescence aptasensor based on the highest affinity aptamer named SA07 provided a limit of detection of 0.92 ng/mL with ignorable cross-reactivity with the 27 tested sulfonamides.The developed aptasensor was applied to milk samples,and achieved good accuracy and precision.These results demonstrated that the integration of an aptamer and chemiluminescence in a sensor platform is a promising method for the sensitive,specific,rapid and accurate detection of antibiotic residues of interest in food samples.