The invention discloses a hot-rolled flat plate of large-wall thickness deep-sea pipe steel and a manufacturing method thereof, and belongs to the technical field of low-carbon microalloyed steel. The hot-rolled flat plate comprises, by weight, 0.025-0.045% of C, 0.10-0.35% of Si, 1.10-1.40% of Mn, less than or equal to 0.015% of P, less than or equal to 0.003% of S, 0.04-0.07% of Nb, less than or equal to 0.06% of V, 0.010-0.020% of Ti, 0.15-0.40% of Ni, less than or equal to 0.20% of Cr, less than or equal to 0.08% of Mo, 0.010-0.040% of Al and the balance Fe and unavoidable impurities, wherein a ratio of Al/N is greater than or equal to 2. The manufacturing method comprises the following steps of blast furnace molten iron collection, pre-desulphurization of blast furnace molten iron, smelting by a converter, LF+RH refining, plate blank continuous casting, plate blank heating, rolling by 4300 rolling mill, ACC fast-cooling, stack cooling, sampling and examination, and warehousing and transportation. The hot-rolled flat plate has stable mechanical property indexes, good plasticity-toughness matching and excellent corrosion resistance. The hot-rolled flat plate subjected to UOE molding pipe-preparation has performances reaching to an X70 level.