As one kind of cheap, environmentally-friendly and efficient treatment materials for direct control of cyanobacterial blooms, modified clays have been widely concerned. The present study evaluated cyanobaterial removal by a red soil-based flocculant (RSBF) with a large enclosure experiment in a tropical mesotrophic reservoir, in which phytoplankton community was dominated by Microcystis spp. and Anabaena spp. The flocculant was composed of red soil, chitosan and FeCl 3. Twelve enclosures were used in the experiment: three replicates for each of one control and three treatments RSBF 15 (15 mg FeCl 3 l −1), RSBF 25 (25 mg FeCl 3 l −1), and RSBF 35 (35 mg FeCl 3 l −1). The results showed that the red soil-based flocculant can significantly remove cyanobacterial biomass and reduce concentrations of nutrients including total nitrogen, nitrate, ammonia, total phosphorus, and orthophosphate. Biomass of Microcystis spp. and Anabaena spp. was reduced more efficiently (95%) than other filamentous cyanobacteria (50%). In the RSBF 15 treatment, phytoplankton biomass recovered to the level of the control group after 12 days and cyanobacteria quickly dominated. Phytoplankton biomass in the RSBF 25 treatment also recovered after 12 days, but green algae co-dominated with cyanobacteria. A much later recovery of phytoplankton until the day of 28 was observed under RSBF 35 treatment, and cyanobacteria did no longer dominate the phytoplankton community. The application of red soil-based flocculant greatly reduces zooplankton, especially rotifers, however, Copepods and Cladocera recovered fast. Generally, the red soil-based flocculant can be effective for urgent treatments at local scales in cyanobacteria dominating systems.