Expanding　pore　size　range　of　metal-organic　frameworks(MOFs)promotes　their　versatility　and　feasibility　for　various　biomedical　applications.However,natural　pore　size　greatly　restricts　large　guest　molecule　accommodation.Customizing　and　tailoring　pore　apertures　ranging　from　micropores　to　mesopores　controllably　is　desired　but　still　critically　challenging.Herein,we　developed　a　facile　method　with　super　mildness　based　on　pH-sensitive　zeolitic　imidazolate　framework(ZIF)-8　to　increase　porosity,providing　pore　size　with　maximum　20　nm,which　is　8　times　larger　than　average.Glucose　oxidase(GOx)was　introduced　in　ZIF-8　for　bio-etching,benefitted　from　the　resultant　acidic　microe-nvironment　during　biocatalytic　process.Different　synthesis　methods　were　assessed　for　obtaining　different　morphologies　and　size　distributions.Reaction　time,GOx　encapsulation　efficiency,and　Zn2+concentration　was　optimized　to　precisely　control　the　mesopore　size　distribution　of　MOFs.It　was　found　that　bio-etching　strategy　was　capable　of　producing　stable　mesopores　which　were　large　enough　for　loading　lactase　with　good　enzymatic　activity　retained,verified　both　in　vitro　and　in　vivo.This　strategy　breaks　natural　pore　size　limitation　of　MOFs　and　thereby　facilitates　biomolecule　delivery,catalysis,and　other　biomedical　applications　with　enhanced　stability　and　performance.