The invention discloses a hole-milling clamping device for an eccentric upper sealing head flange. The hole-milling clamping device comprises a positioning ring, a positioning disc, air cylinders, electromagnetic valves and pressing heads, a set of circular-arc-shaped side walls and an eccentric positioning pin are arranged on the positioning disc, the circular-arc-shaped side walls form a cylindrical excircle, the inner-side surface of each circular-arc-shaped side wall and an end-portion plane are connected through a bevel, two bevels form a conical face, and the air cylinders extend and contract to drive the pressing heads to press or release a workpiece. By utilizing the hole-milling clamping device, processing of an axis hole, four through holes and a strip-shaped hole can be completed on a milling machine, and a sealing plate is clamped only once during processing, so that processing efficiency is improved; the sealing plate is fixed in position and quite easy to clamp, so that aligning difficulty is lowered, and inaccuracy in clamping is avoided; a reference is taken as a processing reference of the side walls, the four through holes and the strip-shaped hole, so that high uniformity is maintained, qualification rate of finished products is increased, and the finished product qualification rate is increased to be more than 97%.