Presently, it is a great challenging issue to inhibit the regeneration for dioxin and simultaneously detoxify Municipal solid waste incinerators (MSWI) fly ash with conventional Hagenmaier pyrolysis process (250–400 °C). The addition of inorganic S- and/or N-containing dioxin inhibitors could effectively inhibit the catalytic roles of residual heavy metals (HMs; e.g. Cu, Pb) for formation pathway of dioxin. In this study, we conducted a newly-proposed single-mode Microwave (MW)-based Hagenmaier process to investigate the impact of N, S-containing inhibitors of Thiourea (TU) on inhibiting the catalytic roles of targeted HMs and simultaneously detoxifying fly ash as well as to elucidate the corresponding mechanism. Synchrotron radiation analysis verified the sulfidation of targeted HMs including Cu and Pb, indicating the inhibition routes for dioxin regeneration. Moreover, the pyrolysis products of TU could apparently increase the MW-absorption properties of fly ash layer, and shorten by ~81.5% of processing time compared with that in the absence of TU. Under the optimized conditions (pyrolysis temperature of 480 °C, a mass ratio of fly ash to SiC as 1:9 and the addition of 23.1 wt% TU), ~99.2% of dioxin and ~94.1% of the bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent values (Bio-TEQs) were eliminated. Furthermore, the fundamental mechanism of a single-mode MW-induced Hagenmaier process was also proposed in detail. Additionally, a series of Unintentionally-Produced Persistent Organic Pollutants (UP-POPs) including chlorobenzenes were also detoxified by a single-mode MW-based Hagenmaier pyrolysis process, simultaneously. To the best of our knowledge, this is the first report adopting TU to inhibit the regeneration of dioxin and simultaneously detoxify fly ash by a single-mode MW-based pyrolysis process.