Materials containing the unreactive elements are attracting increasing attention for their unexpected characteristics like pressure-driven superconductivity. However, the known helium-incorporating superconductors (HISCs) are constrained by extreme compression, and thus achieving high-temperature superconductivity in helium-based compounds under moderate pressure is a key challenge. Here, we conducted a comprehensive study for the Na2He-B system leveraging a first-principles assisted configuration prediction method and presented two previously unknown stable phases, encompassing P63/mmc Na2HeB2 and Immm Na2HeB7. In particular, Na2HeB2 manifests a prototype hexagonal layered structure featuring interlayer sodium-helium co-insertion and a honeycomb-shaped covalent boron grid. Remarkably, calculations of electron–phonon coupling (EPC) uncover that, among HISCs, Na2HeB2 holds the highest superconducting transition temperature (Tc) at a low pressure of 20 GPa, reaching 38 K, which is primarily traced to the coupling of in-plane B 2p electronic states at the Fermi level and Na- and He-governed low-frequency phonon modes. In contrast, the strategy of enhancing the EPC strength through electronic doping (-0.04 e/cell) enabled Na2HeB2 to exhibit high-Tc behavior at 42 K. These findings provide important implications for the discovery of novel superconductors composed of inert elements.