Tetracycline abuse has been a significant threat to human health and the environment. In order to treat the tetracycline residue in water effectively, the metal–organic framework MIL-68(In) and its derivative MIL-68(In)-NH₂ were proposed to photocatalytically degrade tetracycline for the first time and were synthesized by a simple solvothermal method. The structure, morphology, and composition of MIL-68(In) and MIL-68(In)-NH₂ and their photocatalytic properties were investigated by XRD, SEM, XPS, PL, and electrochemical techniques. The comparative experimental results showed that the photocatalytic degradation efficiency of MIL-68(In)-NH₂ was nearly two times higher than that of MIL-68(In) under simulated sunlight (280 nm < λ < 980 nm) irradiation, indicating that the amino group played an important role in photoexcitation. Free radical capture experiments demonstrated that the main active substances of MIL-68(In)-NH₂ are O₂⁻ and h⁺, which reacted with tetracycline directly. The results of this work can contribute to the design of photocatalysts and the understanding of the photocatalytic degradation of the residue of antibiotics in water and the corresponding mechanism.