A dual recognition system with a fluorescence quenching of quantum dots (QDs) and specific recognition of molecularly imprinted polymer (MIP) for the detection of chloramphenicol (CAP) was constructed. MIP@SiO@QDs was prepared by reverse microemulsion method with 3-aminopropyltriethoxysilane (APTS), tetraethyl orthosilicate (TEOS) and QDs being used as the functional monomer, cross-linker and signal sources, respectively. MIP can specifically recognize CAP, and the fluorescence of QDs can be quenched by CAP due to the photo-induced electron transfer reaction between CAP and QDs. Thus, a method for the trace detection of CAP based on MIP@SiO@QDs fluorescence quenching was established. The fluorescence quenching efficiency of MIP@SiO@QDs displayed a desirable linear response to the concentration of CAP in the range of 1.004.00 × 10 μmol × L, and the limit of detection was 0.35 μmol × L (3σ, = 9). Importantly, MIP@SiO@QDs presented good detection selectivity owing to specific recognition for CAP, and was successfully applied to quantify CAP in lake water with the recovery ranging 102.0104.0%, suggesting this method has the promising potential for the on-site detection of CAP in environmental waters.