Single-phase multiferroic materials are usually considered useless because of the weak magnetoelectric effects, low operating temperature, and small electric polarization induced by magnetic orders. As a result, current studies on applications of the magnetoelectric effects are mainly focusing on multiferroic heterostructures and composites. Here we report a room-temperature giant effect in response to external magnetic fields in single-phase multiferroics. A low magnetic field of 1000 Oe applied on the spin-driven multiferroic hexaferrites BaSrCo2Fe11AlO22 and Ba0.9Sr1.1Co2Fe11AlO22 is able to cause a huge change in the linear magnetoelectric coefficient by several orders, leading to a giant magnetotranstance (GMT) effect at room temperature. The GMT effect is comparable to the well-known giant magnetoresistance (GMR) effect in magnetic multilayers, and thus opens up a door toward practical applications for single-phase multiferroics.