The disclosure relates to a system and method for calibrating a medical system. The method may include one or more of the following operations. Projection data of a phantom comprising a plurality of markers may be acquired from an imaging device, at a plurality of angles of a source of the imaging device. A plurality of projection matrices of a first coordinate system relating to the phantom and a transformation matrix between the first coordinate system and a second coordinate system relating to the imaging device may be determined based on the projection data of the phantom and coordinates of the plurality of markers in the first coordinate system. A plurality of projection matrices of the second coordinate system may be determined based on the plurality of projection matrices of the first coordinate system and the transformation matrix.