Lithium niobate (LiNbO3) is a material that has drawn great interest in nonlinear optics because of its large nonlinear susceptibility and wide transparency window. However, for complex nonlinear processes such as high-harmonic generation (HHG), which involves frequency conversion over a wide frequency range, it can be extremely challenging for a bulk LiNbO3 crystal to fulfill the phase-matching conditions. LiNbO3 metasurfaces with resonantly enhanced nonlinear light-matter interaction at the nanoscale may circumvent such an issue. Here, we experimentally demonstrate efficient second-harmonic generation (SHG) and HHG from a LiNbO3 metasurface enhanced by guided-mode resonance. We observe a high normalized SHG efficiency of 5.1 × 10-5 cm2 GW-1. Moreover, with the alleviated above-gap absorption of the material, we demonstrate HHG up to the 7th order with the shortest generated wavelength of 226 nm. This work may provide a pathway towards compact coherent white-light sources with frequency spanning into the deep ultraviolet region for applications in spectroscopy and imaging.