The crystalline structures of lanthanum tetraboride, LaB4, under pressure are investigated using a genetic algorithm method coupled with first-principles calculations. We investigate the phase transitions of LaB4 up to 200 GPa and find a novel orthorhombic phase (Pnma-I). The P4/mbm phase transforms to the Cmmm phase at around 85 GPa, and then to Pnma-I phase at 133 GPa. The P4/mbm phase of LaB4 exhibits a high hardness at ambient conditions. The hardness of the P4/mbm, Cmmm, and Pnma-I phases increases with pressure. The increased B–B bond contributes to the enhanced hardness of LaB4. The electronic band structures shows that all of the competitive phases (three stable and two metastable phases) are metallic. This elucidation of the phase transition behavior and hardness of LaB4 provides new knowledge on the interesting high-pressure behaviors of the rare-earth metal borides.