In this work, a novel sandwich-type hybrid denoted as MPZSN-MoS2 was constructed by the self-assembling of melamine, phytic acid and Zn2+ to grow 2D supermolecular networks (MPZSN) onto the surface of molybdenum disulfide (MoS2) nanosheet, which was applied in mechanical and flame-retardant reinforcements of polyacrylonitrile fiber. With the incorporation 2 wt% MPZSN-MoS2, the tensile strength and elongation at break of MPZSN-MoS2/PAN composite fiber were increased by 68.2% and 27.8% compared to pure PAN fiber, respectively. The initial thermal decomposition temperature (T-5%) of MPZSN-MoS2/PAN fiber was increased by 21 degrees C, suggesting the enhanced thermal stability. Importantly, the single MPZSN-MoS2/PAN composite fiber could not be ignited and exhibited noticeable char formation when directly exposed to a flame, while the pure PAN fiber caught fire immediately and burned out. Moreover, the peak heat release rate and total heat release of MPZSN-MoS2/PAN fiber were remarkably decreased by 49.9% and 38.1% in contrast to pure PAN fiber, indicating its superior fire performance. The gaseous and condensed analysis demonstrated that the addition of MPZSN-MoS2 hybrids inhibited the effusion of pyrolysis products, such as HCN, CO, aliphatic CeH compounds, C=C compounds and carbonyl compounds, and promoted the generation of graphitized protective char layer on the fiber surface. This work presents a facile strategy for the design of MoS2-based hybrids with multi-components, expanding their potential applications in polymer composites.