Nuclear reactions between protons and boron-11 nuclei (p–B fusion) that were used to yield energetic α-particles were initiated in a plasma that was generated by the interaction between a PW-class laser operating at relativistic intensities (~3 × 1019 W/cm2) and a 0.2-mm thick boron nitride (BN) target. A high p–B fusion reaction rate and hence, a large α-particle flux was generated and measured, thanks to a proton stream accelerated at the target’s front surface. This was the first proof of principle experiment to demonstrate the efficient generation of α-particles (~1010/sr) through p–B fusion reactions using a PW-class laser in the “in-target” geometry.