In this study, the structural integrity of an engine-generator support structure of hybrid drone is verified through finite element (FE) analysis and experimental investigation. From preliminary experiments, critical failures in four columns of the support structure were observed. Due to the repeated cyclic loads induced by the engine-generator operation, the results of the FE simulation pointed out that fatigue failure is the main cause. To improve the structural integrity, the geometric shape and the material of the structural members are modified and changed, and the safety factor is also reviewed using static structural analysis. The possibility of critical resonance is evaluated through FEM-associated modal analysis and a series of vibration tests. As result, it is confirmed that the re-designed support structure was structurally improved with enough safety margin through FE analysis and experimental investigation, and fatigue life by comparing the predicted value and S-N curve of the material used to the support structure was improved.