Due to the rapid development of phasor measurement units (PMUs) and the wide area of interconnection of modern power systems, the security of power systems is confronted with severe challenges. A novel framework based on data for static voltage stability margin (VSM) assessment of power systems is presented. The proposed framework can select the key operation variables as input features for the assessment based on partial mutual information (PMI). Before the feature selection procedure is completed by PMI, a feature preprocessing approach is applied to remove redundant and irrelevant features to improve computational efficiency. Using the selected key variables, a voltage stability assessment (VSA) model based on iterated random forest (IRF) can rapidly provide the relative VSM results. The proposed framework is examined on the IEEE 30-bus system and a practical 1648-bus system, and a desirable assessment performance is demonstrated. In addition, the robustness and computational speed of the proposed framework are also verified. Some impact factors for power system operation are studied in a robustness examination, such as topology change, variation of peak/minimum load, and variation of generator/load power distribution.