In this study, a rapid and sensitive electrochemical sensor (ZnCo2O4@NC) based on metal-organic frame (MOF)-derived metal oxide material (ZnCo2O4) and chitosan derived nitrogen-doped carbon material (NC) was successfully constructed for the simultaneous determination of acetaminophen (APAP) and p-aminophenol (PAP). A series of electrochemical experiments proved that the MOF derived ZnCo2O4@NC composite has excellent electrochemical response to APAP and PAP in the phosphate buffer saline (PBS) (pH 7.0). The current response varies linearly with the increase of APAP concentration in the range of 8.0 μmol L−1 to 520 μmol L−1 and PAP concentration in the range of 6.0 μmol L−1 to 420 μmol L−1. The sensitivity and limit of detection (LOD) of ZnCo2O4@NC for APAP and PAP detection are 0.1024 and 0.2749 μA μmol L−1 cm−2, 0.0608 and 0.2489 μmol L−1, respectively. The ZnCo2O4@NC composite modified electrode exhibits good selectivity, reproducibility and stability. Additionally, in the detection for acetaminophen sustained-release tablets, the recovery rates of APAP are in the range of 90.00 % –100.00 %. The theoretical content is consistent with our detection results, showing that this method has good accuracy in actual sample analysis. This study provides an innovative idea to improve electrochemical performance of simultaneous detection of acetaminophen and p-aminophenol through the comprehensive strategy of structural design, heteroatom doping.