The effects of penetrating holes on the tensile properties of titanium honeycomb panels with variable cross-section used in aircraft structure was studied experimentally and numerically. Among them, the finite element model included the details of the honeycomb core and the detailed structure of the bevel area was established by parametric modeling method. The results showed that the bevel area was the weak part of the titanium honeycomb panels with variable cross-section, the failure mode of the specimen without hole was the cross section fracture along the chamfer of the skin in the initial area of bevel. For the panels with penetrating hole, there was a diameter threshold of 40mm. When the penetrating hole diameter was less than the threshold, the failure mode and tensile fracture load of the panels with penetrating hole were consistent with the panels without hole. When the penetrating hole diameter exceeded the threshold, the failure mode of the panels with penetrating hole changed to fracture along the cross-section of penetrating hole and the tensile fracture load decreased linearly with the increase of the diameter of penetrating hole.