The present invention discloses a high-resistivity single crystal zinc oxide (ZnO) wafer and a high-resistivity single crystal ZnO-based radiation detector, and preparation method and use thereof. The preparation method of the high-resistivity single crystal zinc oxide wafer is to place a single crystal ZnO wafer in a metal lithium electrochemical device for a constant-current discharge treatment, and then to place the single crystal ZnO wafer in a high-pressure oxygen atmosphere at 800 to 1000° C. and 10 to 30 atm for an annealing treatment for 20 to 28 hours. The preparation method of the radiation detector is to evaporate a metal electrode layer at both sides of the high-resistivity single crystal ZnO wafer, then to bond the wafer onto a circuit board, and to connect the wafer with the circuit board by a gold thread.