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Recently, tube potential selection methods of variable energy imaging have not taken the acquired images’ information into consideration, and can not select the potential intelligently and quickly. This paper proposes an Optimum Tube Potential Prediction Method based on variable energy imaging. The method has four steps. First of all, scan the object to obtain image sequence of variable potential. Secondly, find the effective thickness(ET)(high quality area) and near the effective thickness (NET)(low quality area), and the relationship between them and tube potential. Thirdly, build a function model of potential and image gray difference between ET and NET, thus get the optimal potential prediction model of NET. Finally, search the optimal potential for NET based on the two models. At the end of paper, collect graded voltage image sequence of steel blocks with different thickness, then use the method to predict optimal potential for each thickness and compare them with the actual one. Experimental results showed that this method can accurately predict 3 or 4mm at low potential and 7 or 10mm at high potential. Prediction accuracy can reach over 95%.