A plasma colorimetric aptasensor was developed for rapid determination of chloramphenicol (CAP) in honey on site. Herein, cage gold shell@core nanoparticles (Au@AuNPs) were synthesized to enhance signal response and broaden the linear range. In addition, aptamer-based cascade hybridization chain reaction (cHCR), consisting of HP1, HP2, HP3, and HP4, was also designed for signal amplification and specific analysis. In this assay, HP1 and HP4 were immobilized on the surface of cage Au@AuNPs. In the presence of CAP, cHCR was triggered, and frond-like DNA products were formed, which made the distance among the cage Au@AuNPs closer and the system color changed from red to deep purple. Qualitative and quantitative analysis were carried out according to color changes and UV-Vis spectra. Under the optimized conditions, the wavelength of UV-Vis absorption peak exhibited a good linear relationship with CAP concentration in the range of 5.0 to 500 nmol/L with the detection limit of 1.2 nmol/L (S/N = 3). This aptasensor also showed good specificity for CAP detection compared with other antibiotics similar to the target analyte. Furthermore, the colorimetric aptasensor was successfully applied to the detection of CAP in honey with recoveries of 88.0-107.6%. This cHCR-based aptasensing for CAP possesses high sensitivity, good selectivity, low cost and excellent stability, and could be extended to detect a wide variety of other small molecular analytes, nucleic acids or proteins. Therefore, the versatile method might become a potential alternative tool in food analysis and environmental monitoring.Copyright © 2022 Elsevier Ltd. All rights reserved.