Single-crystalline ordered macro-microporous CuBTC shows excellent mass transfer performance and has high fatty acid stability, making it highly promising as an enzyme immobilization carrier. However, its practical application is severely limited by its poor water stability. To address this challenge, we introduced a ligand, 1,2,3-benzotriazole (BTA), known for its hydrophobicity and strong coordination with copper. A series of CuBTCderived dual-ligand SOM-MOFs (SOM-MIXs) was successfully synthesized with enhanced hydrophobicity and improved water stability. The CuBTCderived SOM-MIXs demonstrated superior performance for lipase immobilization, resulting in a maximum increase of 66.9% in specific activity. To address the limitation that excessive addition of 1,2,3-benzotriazole does not further enhance the hydrophobicity of the carrier and may lead to structural damage, a sol−gel method was employed to coat the SOM-MIX with highly hydrophobic PDMS, leading to a further increase of 139.1% in the specific activity. The resulting immobilized lipase exhibited excellent catalytic performance and remarkable reusability, with 90.09% activity retention after five cycles in the synthesis process of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) by acidolysis. This work highlights the potential of SOM-MIX@PDMS and provides valuable insights into the rational design and postmodification of metal−organic frameworks (MOFs) for enzyme immobilization in diverse applications.