In this contribution, we reported the liquid single-stage synthesis of isoprene from methyl tert-butyl ether (MTBE) and formaldehyde over activated carbon supported silicotungstic acid (STA/AC) catalysts. In comparison with the corresponding homogeneous STA catalysts, the STA/AC catalysts exhibited much higher activity of the prins condensation reaction under the same conditions. The results could be attributed to the highly dispersed STA, the relative weaker acidity resulting from the strong interaction between STA and AC and the structural collapse of STA. Additionally, the catalyst could be reused at least 3 times with only a slight decrease of activity. The physical and chemical properties of the STA/AC catalysts were characterized by means of DRIFT, HRTEM, HAADF-STEM, NH3-TPD, XRD, XPS and TG techniques. The excellent catalytic reactivity and easy recycling advantages make the STA/AC catalyst to be an attractive candidate of the prins reactions in the future.