The separation of $ C_2H_2 $ from $ CO_2 $ is an important process for industrial achievement of gaseous precursor $ C_2H_2 $, which is yet challenged by the well-known trade-off between capacity and selectivity derived from their close physical properties (such as the nearly identical kinetic molecular sizes). Herein, we experimentally screen a series of Hoffman-type metal organic frameworks (MOFs) and regulate the pore size and functionality by introducing different metal cation and organic linkers. We find that among the obtained MOFs, a N $ i^2 $ + based MOF (termed as Ni-Pz) shows the best performance of efficient $ C_2H_2 $ separation from $ CO_2 $, featuring both high capacity (106 c $ m^3 $ /g) and selectivity (10.8). Moreover, to the best of our knowledge, Ni-Pz has never been explored in $ C_2H_2 $ related separation before and is the only MOF that balances the adsorption capacity (>100 c $ m^3 $ /g), selectivity (>10), adsorption heat (<45 kJ/mol) and stability (>400 °C; pH = 1–12). Grand Canonical Monte Carlo (GCMC) simulations reproduce the experimental results and reveal several typical binding configurations of $ C_2H_2 $/ $ CO_2 $ in Ni-Pz. Density functional theory calculations corroborate that the binding configurations from GCMC are very stable and that $ C_2H_2 $ has stronger binding affinity inside the cavity of Ni-Pz than $ CO_2 $. Practical separation performance is further demonstrated by dynamic breakthrough experiments with good recyclability. Overall, our findings highlight that the Ni-Pz MOF screened from various Hoffman-type MOFs is an excellent candidate for industrial application.