Because of the high efficiency of frequency conversion and beam–target coupling, a fourth harmonic (4ω) laser has a splendid application prospect in a high-power laser facility. The polarization smoothing (PS) crystal is preferably after the frequency conversion crystal to flexibly obtain the best uniformity illumination of the target. However, as a high irradiance 4ω laser beam propagates through the PS crystal, the transverse stimulated Raman scattering (TSRS) effect of the PS crystal will be stronger, resulting in significant energy dissipation and crystal damage. This paper proposes a novel, to the best of our knowledge, fourth harmonic generation (FHG) scheme based on an orthogonal cascade of the DKDP crystals. This orthogonal cascaded FHG (OC-FHG) scheme employs two cascaded FHG crystals with orthogonal optical axes, and the PS crystal is in the middle. The PS crystal can rotate the polarization direction of the 2ω laser by 90°, while the polarization direction of the 4ω laser is maintained to a great extent. This OC-FHG scheme realizes the FHG by two steps, and the laser intensity at the PS crystal cuts down nearly 50%. The output intensity of the 4ω laser can be increased from 1.8GW/cm2 to about 3.6GW/cm2 under the condition of effectively inhibiting the TSRS effect. Meanwhile, the output 4ω laser contains two orthogonal polarized beams realizing in-beam polarization smoothing instantaneously. In addition, the novel FHG scheme can also have a high conversion efficiency and bandwidth tolerance.