Molecular stratigraphical, carbonate carbon isotopic, stratigraphical and paleontological data show that algal booming, eutrophication, anoxia, hypersalinity, positive δ13C excursion and biomass decreasing occurred in the offshore carbonate environments of the Frasnian-Famennian (F-F) transition, which hints that red tide might frequently take place in the F-F transition of Guangxi, South China. We suggest that the mass extinction of the reef ecosystems and the shallow-water marine organisms in the F-F transition of the lower-middle latitudes may be related to the frequent occurrence of red tide in that time. Molecular stratigraphical, carbonate carbon isotopic, stratigraphical and paleontological data show that algal booming, eutrophication, anoxia, hypersalinity, positive δ13C excursion and the amount of this issue to the Frasnian-Famennian (FF) transition, which hints that red tide might frequently take place in the FF transition of Guangxi, South China. We suggest that the mass extinction of the reef ecosystems and the shallow-water marine organisms in the FF transition of the lower-middle latitudes may be related to the frequent occurrence of red tide in that time.