The invention relates to a process for manufacturing a large-caliber thick-wall seamless steel tube, in particular to a method for manufacturing a large-caliber thick-wall seamless steel tube in a vertical extrusion way, belonging to the field of iron and steel manufacture. The method comprises the following steps of: cutting a riser and an ingot tail of a steel ingot, removing scales and oxide coating of the heated steel ingot by using high-pressure water, and spraying glass lubricant; making the steel ingot into a hollow blank, hot-grinding and hot-finishing, removing scales and oxide coating of the hollow blank subjected to hot finishing by using high-pressure water, and spraying glass lubricant; extruding the hollow blank into a pipe blank, and removing residual glass membranes by adopting an inner shot-blasting device and an outer shot-blasting device; heat-treating, fine-finishing and detecting. By combining the working procedures of removing scales by using the high-pressure water, spraying the glass lubricant and hot-finishing the hollow blank with the original working procedures, the invention can effectively reduce the die loss, save the energy and improve the working efficiency.