Since acetaminophen (ACAP) and 4-aminophenol (4-AP, the degradation product from ACAP) have different properties and toxicities, the simultaneous electrochemical determination of ACAP and 4-AP is very important. In this work, nitrogen-doped hollow carbon spheres wrapped with MoS2 nanosheets (MoS2@NHCSs) novel hybrids were synthesized via a simple step-by-step method and consecutively the obtained MoS2@NHCSs was successfully used to construct a reliable electrochemical sensor for simultaneously detecting acetaminophen (ACAP) and 4-aminophenol (4-AP). Owing to the synergetic properties of each component in MoS2@NHCSs nanohybrids (MoS2 has highly catalytic activity and can offer many active sites; NHCSs can impede the aggregation tendency and enhance the effective surface area of MoS2 as well as increasing the conductivity of the nanohybrids), the experimental results demonstrated that the electrochemical responses of both 4-AP and ACAP at MoS2@NHCSs modified electrode are much better than those at NHCSs or MoS2 modified electrodes. Importantly, the MoS2@NHCSs nanohybrids can show excellent electrochemical sensing performance for the sensitive and selective as well as simultaneous determination of ACAP and 4-AP. After optimizing various conditions, the proposed MoS2@NHCSs-based sensor has wide linear range and low detection limit for ACAP and 4-AP analysis.