The photo-induced peroxymonosulfate (photo-PMS) reaction is a promising route to eliminate antibiotics from waste water. To achieve excellent photo-PMS activity in Mg–Fe layered double hydroxides (LDHs) for tetracycline hydrochloride (TCH) degradation under simulative solar-light irradiation, Mg–Fe LDHs-loaded polyacrylonitrile (Mg–Fe/PAN) nanofibers were in-situ prepared via the hydrothermal route. For comparison to the photocatalysis and photo-PMS process, the Mg–Fe/PAN-assisted photo-PMS process exhibited a better elimination activity for TCH elimination. In addition, the photo-PMS activities of Mg–Fe/PAN composites were greatly affected by Mg–Fe LDHs content, TCH concentration, pH, and inorganic salts. Among these Mg–Fe/PAN composites, the optimal MgFe2/PAN with a Mg/Fe molar ratio of 1:2 and a nominal Mg–Fe LDHs content of 2.0 wt. % removed 81.31% TCH solution of 80 mg L−1 TCH within 120 min. This enhanced photo-PMS capacity of MgFe2/PAN was ascribed to the abundant active sites formed by functional groups and oxygen defects for efficient TCH species adsorption and photon capturing, and the tight interface between Mg–Fe LDHs nanoparticles and PAN nanofibers for the rapid separation and transfer of photoinduced e−/h+ pairs. SO4•− and •O2− radicals were vital for the MgFe2/PAN-assisted photo-PMS reaction.