The extensive utilization of rigid polyurethane foam (RPUF) as construction insulation material has brought two main troubles to our society: fire risks and toxic hazards. To reduce the fire hazards of RPUF, a layered MoS decorated with CuO nanoparticles was creativity obtained by hydrothermal technology and facile wet chemical treatment for reducing the toxic product formations of polyurethane nanocomposites during combustion. Due to the low weight ratio of CuO attached onto MoS, the resulting CuO-MoS hybrid effectively prevented the MoS nanosheets from restacking. However, the CuO-MoS-M hybrid was produced by increasing content of CuO, which has the characteristic stacked layer structure of MoS. Reduced harmful organic volatiles and the toxic gases (e.g. a respective decrease of ca. 28% and 53% for CO and NO products) were obtained because of synergistic effect between the physical adsorption of MoS and catalysis action of CuO. Notably, the addition of CuO-MoS hybrids led to high char formation of the RPUF nanocomposite, indicating the effectively catalytic carbonization property. In addition, the N-Gas model for predicting fire smoke toxicity was developed and demonstrated. Furthermore, the research offers direct proofs of the negative influence of the stacked MoS on reducing the smoke toxicity for RPUF nanocomposites.