Considering the tremendous applications and purification requirement of acetylene (C₂H₂), seeking appropriate adsorbents with high capacity and selectivity is a vital task and remains an enduring challenge. Herein, we designed and synthesized a robust three-dimensional (3D) indium-organic framework ([(Me)₂NH₂][In(L₆)_0.5(IPA)_0.5]·DMA·2H₂O (In-L₆-IPA, DMA = dimethylammonium, IPA = isopropyl alcohol)) featuring two types of one-dimensional (1D) tubular channels. The activated In-L₆-IPA displayed high loading for C₂H₂ (104.4 cm³·g⁻¹, the second highest value among all reported indium-based metal-organic frameworks (MOFs)) and simultaneously selective adsorption for C₂H₂ over CO₂, C₂H₆, and ethylene (C₂H₄) at 298 K under 100 kPa. Molecular modelling revealed that the porous wall of In-L₆-IPA provides more and stronger multiple interactions for C₂H₂ than CO₂, C₂H₆, and C₂H₄ containing C–H···π, C–H···O, and O···π interactions. Breakthrough experiments validated the actual separation ability for various ratios of binary C₂H₂/C₂H₄ and C₂H₂/CO₂ mixtures as well as equimolar ternary C₂H₂/C₂H₄/CO₂ and C₂H₂/C₂H₄/C₂H₆ mixtures with excellent reusability.