Toxic 4-aminophenol (4-AP) can be considered as a primary impurity during the synthesis and/or storage of N-acetyl-para-aminophenol (APAP). In this study, 4-AP was sensitively and selectively detected in the presence of APAP using a gold.silver core-shell nanoparticle-embedded silica nanostructure (SiO2@Au@Ag). First, approximately 200 nm of SiO2@Au@Ag were successfully prepared based on the Au-seed (3 nm) mediated growth of Ag on the surface of SiO2 NP. Upon the incubation of 4-AP with SiO2@Au@Ag nanoparticles (NPs), the surface-enhanced Raman spectroscopy (SERS) intensity of 4-AP at 1591 cm-1 increased proportionally in accordance with an increase in the concentration of 4-AP in the range of 0-800 μM, with a detection limit of 3.5 ppm. In addition, the APAP did not exhibit a significant Raman signal at high concentrations (5 mM) and under the NP incubation condition. In the presence of 1 mM, 3 mM, and 5 mM of APAP, 4-AP was detected using SiO2@Au@Ag NPs within the rangeof 200-1000 mM, although the slopes decreased from 0.083 cps/mM to 0.059 cps/μM, 0.068 cps/μM, and 0.035 cps/ μM, respectively. This study provides a method for the detection of 4-AP in the presence of APAP by using SiO2@Au@Ag for impurity detection in the pharmaceutical field.