Magneto-transport study has been performed in topological semimetal ZrSiS single crystals under high pulsed magnetic fields. Obvious dependence of Landau level splitting on temperature and angular was investigated. The strong three-dimensional anisotropic nature of Landau level splitting under high pulsed magnetic fields was revealed by the angular dependent measurements, in which the orbital contribution is more dominant than Zeeman splitting. Our studies provide more insights into the physical properties of topological semimetals ZrSiS and shed light on future spintronic applications of ZrSiS.