Acquiring helium gas (He) via membrane separation technology is deemed a prospective and benign approach to mitigate the He shortage crisis. This study demonstrates, through theoretical means, that the recently synthesized r-N-GY nanostructure can serve as a semipermeable membrane for highly efficient separation of He and its isotopes. Our simulation results clearly reveal that the r-N-GY monolayer exhibits an excellent selectivity in separating He from natural gas molecules, with a selectivity exceeding 10 8 toward He over other impurities. Additionally, the He permeance reaches 1.1 × 10 −5 mol s −1 m −2 Pa −1 , surpassing the industrial standard by 4 orders of magnitude. We further demonstrate that the application of tensile strain can effectively regulate He permeance. For instance, the application of 8% strain along the armchair (AC) direction results in the substantial reduction in the energy barrier for gas molecules passing through the r-N-GY monolayer, leading to a two-order-of-magnitude increase in He permeation rate compared to that of the unstrained case, while still maintaining ultra-high He/Ne and He/N 2 selectivity (10 3 and 10 15 , respectively). Moreover, there is a marked enhancement for the quantum sieving of 3 He/ 4 He upon application of 8% tensile strain along AC direction, thus offering a promising strategy for both He and 3 He isotope separation. Therefore, this study suggests a high performance and strain-tunable nanostructure candidate with great promise in He and He isotope purification that can constitute the ultimate functions of nanomaterials in semi-permeable membrane technique.