An ultrasensitive label-free electrochemical immunosensor using MoS2/NiCo heterostructures as an efficient signal enhancer was proposed for sensitive detection of procalcitonin. The MoS2/NiCo heterostructures were synthesized by thermally depositing MoS2 on NiCo MOFs nanocubes, which were then functionalized with in situ grown palladium nanoparticles (Pd NPs) for electrochemically catalyze the reduction of hydrogen peroxide. The presence of MoS2/NiCo heterostructures greatly enhanced the electrocatalytic activity of Pd NPs, thus the Pd NPs@MoS2/NiCo modified electrode showed amplified response to hydrogen peroxide. The large specific surface of Pd NPs@MoS2/NiCo greatly improved the loading of antibody for preparation of immunosensor. Upon the incubation of the immunosensor with target procalcitonin, the electron transfer impendence increased, and thus the chronoamperometric response decreased, leading to a highly sensitive immunosensing method for detection of procalcitonin. The proposed method showed a linear range of 0.001–50 ng/mL with a detection limit of 0.36 pg/mL (S/N = 3). It possessed excellent accuracy and good practicality for diagnostics of PCT related diseases, and could be extended for development of other immunosensors for biomarkers detection.