The invention belongs to the technical field of low-alloy high-strength steel, and particularly relates to a thick steel plate suitable for large heat input welding in EH420 grade marine engineering and a preparation method of the thick steel plate. The steel plate comprises the following chemical components of, by mass percentage, 0.05-0.12% of C, 0.1-0.3% of Si, 1.0-1.7% of Mn, 0.001-0.01% of P,0.001-0.005% of S, 0.01-0.04% of Nb, 0.005-0.025% of Ti, 0.2-0.5% of Cu, 0.2-0.5% of Ni, 0.001-0.006% of N, 0.001-0.005% of O, 0.005-0.025% of Al, 0.0005-0.005% of Mg, 0.0005-0.005% of Ca and the balance of Fe. Al-Mg-Ti-Ca-Mn-O-S composite inclusions account for more than 10% of inclusions with the sizes of 0.5-5 [mu]m in the steel plate and have special compositions. The steel plate is preparedaccording to the steps of adding silicon and manganese when steel is discharged from a converter, and feeding calcium wires, titanium wires, magnesium wires and aluminum wires during LF and RH refining; and adopting two-stage controlled rolling and controlled cooling. Particles of the inclusions in the steel plate are favorable for fine dispersion and distribution, have a better capability of promoting acicular ferrite nucleation, and can obviously improve low-temperature toughness of large heat input welding.