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CuInS₂/Mg(OH)₂ (CIS/Mg(OH)₂) nanosheets have been prepared for the visible light activated photodegradation of tetracycline hydrochloride (TCH). The introduction of CuInS₂ has proven to enhance the photocatalytic activity of Mg(OH)₂ nanosheets. It’s ascribed to the enhanced transfer and separation of charge carriers at the junction interface between CuInS₂ and Mg(OH)₂. The photocatalytic activity of obtained CIS/Mg(OH)₂ is greatly affected by CuInS₂ content, pH value, and inorganic ions. Among these samples, 2-CIS/Mg(OH)₂ exhibits the excellent photocatalytic activity and durability for the visible light driven removal of TCH after five cycle times. Atomic force microscope (AFM) images indicate that the surface roughness of 2-CIS/Mg(OH)₂ is intensively influenced in adsorption-photocatalysis process. The •O₂^− and •OH radicals are vital for the visible light driven photocatalytic activity of 2-CIS/Mg(OH)₂ for TCH removal.