Abstract: ⁶⁸Ge is the parent nuclide of radioactive nuclide ⁶⁸Ga used in positron emission tomography (PET) diagnostic imaging, which is converted into ⁶⁸Ga by a ⁶⁸Ge/⁶⁸Ga generator for clinical diagnostic imaging applications. Currently, there are 13 kinds of ⁶⁸Ga labeled radiopharmaceuticals in China that have entered clinical practice and have good application prospects in tumor imaging such as high-grade endocrine tumors and prostate cancer. Therefore, with the approval and widespread use of ⁶⁸Ga radiopharmaceuticals, ⁶⁸Ge has broad application prospects in both domestic and international markets.In addition,⁶⁸Ge can also be widely used as a calibration source for PET scanners.China Institute of Atomic Energy (CIAE) plans to build a 75 MeV cyclotron with the maximum beam current of 800 μA and the proton energy range of 75 MeV. It will be used to focus on the production of ⁶⁸Ge nuclide.This article used the Monte Carlo program FLUKA to simulate in detail the production of ⁶⁸Ge nuclides yield, reaction products, the variation of impurity nuclide production with cooling time, and long-life nuclides affecting separation processes by irradiating gallium nickel alloy targets and niobium gallium capsule targets in medium to high energy proton cyclotron.The simulation results can provide the useful reference for the production, separation, and purification of ⁶⁸Ge in medium to high energy cyclotron.