This article investigates in depth the conditions for cleaning of the (100) ZnSe substrate surface for ZnSe homoepitaxial growth. Wet etching with a K2Cr2O7-based etchant as a pre-growth treatment is found to result in a Se-rich ZnSe surface that retains its original flatness. Reflection high energy electron diffraction patterns show that plasma irradiation during thermal cleaning is indispensable for removing the oxide layer on ZnSe substrate and keeping the flatness. In hydrogen plasma cleaning, the etch pit density (EPD) of the homoepitaxial film increases at rf power higher than 265 W, indicating the optimum cleaning temperature is between 260 and 280 degrees C. As for the dependence of the EPD on the cleaning time, a minimum EPD of 2.7 x 10(4)/cm(2) can be obtained for a plasma cleaning time of 20 min. A correlation between the interfacial residual oxygen concentration and the defect density in an epitaxially grown ZnSe film is also found.