Due to the potential applications in many fields such as thermoelectric, transistor, and electrode materials, a novel two-dimensional layered material TiS3 has attracted tremendous attention recently. In this article, the thickness dependent and anisotropic in-plane thermal transport behavior is explored by first-principles calculation with Boltzmann transport equation. The calculation results show that when the thickness is smaller than phonon confinement size (PCS), the phonon confinement effect is dominant and the in-plane thermal conductivity has a negative dependence on thickness due to the increase of phonon–phonon scattering; when the thickness is larger than PCS, the confinement effect is weak and the dependence becomes positive due to the decrease of phonon–boundary scattering. Through further analysis, we find this non-monotonic dependence or phonon confinement phenomenon is mainly caused by the low-frequency phonons. The calculation results also show strong thermal anisotropy within the basal plane. The coupling strength, bond length, phonon group velocity, dispersiveness of optical phonon branches, iso-energy surface and iso-surface of electron density distribution are analyzed to explain the anisotropy. Based on the 1D diatomic chain model, a unit cell having similar atomic mass and strong intracell bond can enhance the dispersiveness of optical phonon branches. Those findings here can give physical insights into the thickness dependent and anisotropic in-plane thermal transport in layered materials.