A power-switching device with interlock mechanism has a housing with a rotary knob, a slider slidably moved into a rotation range of the rotary knob, and an activation switch mounted on a sliding path of the slider. The activation switch has a control button located on an overlapped portion of the sliding path of the slider and the rotation range of the rotary knob. When the slider approaches the rotary knob, the activation switch is activated and the rotary knob is unable to rotate for being blocked. When the slider departs from the rotary knob, the activation switch is deactivated and the rotary switch is rotatable. Accordingly, when manually bypassing a UPS by turning the rotary knob, users will not forget to deactivate the activation switch, thereby avoiding damaging the UPS.