<p>Human carboxylesterase 1 (hCE1) is a serine hydrolase that is distributed widely in the human liver, intestines, and various tumour tissues. It has now become a biomarker associated with diseases such as cancer. Consequently, the measurement of hCE1 levels in human serum is of significant importance for the diagnosis and assessment of these diseases. The present study involved the preparation of Ag/CQDs/ZIF-8 nanocomposites, which incorporated silver nanoparticles (Ag NPs) and carbon quantum dots (CQDs) into the ZIF-8 framework. The combination of this composite with an enzyme-linked immunosorbent assay (ELISA) and the utilisation of benzidine as the signal molecule resulted in the development of a fluorescence (FL)/surface-enhanced Raman scattering (SERS) dual-mode sensor, which was employed for the sensitive detection of hCE1 in serum. This dual-mode sensor combines the advantages of both FL and SERS technologies, demonstrating excellent selectivity and stability, and enhancing the accuracy and reliability of quantitative measurements. The limits of detection (LOD) for the FL mode and SERS mode were determined to be 0.1 and 0.072 ng·mL^− 1, respectively, with the recoveries ranging from 92.44% to 117.47%. The satisfactory outcomes obtained from testing on real sample confirm the sensor’s excellent suitability for use in complex biological matrices. Consequently, this dual-mode sensor shows considerable promise for the detection of biomolecules in clinical samples, thereby demonstrating significant potential for clinical applications.</p> Graphical abstract <p></p>