Splenectomy　often　accompanies　distal　pancreatectomy　for　pancreatic　cancer.　However,　debates　persist　on　splenic　function　loss　impact.　Prior　studies　in　mice　revealed　splenectomy　promotes　pancreatic　cancer　growth　by　altering　CD4/Foxp3　and　CD8/Foxp3　ratios.　The　effect　on　other　immune　cells　remains　unclear.　Clinical　observations　indicate　splenectomy　induces　immunosuppression,　heightening　recurrence　and　metastasis　risk.　Here,　we　established　an　orthotopic　pancreatic　cancer　model　with　splenectomy　and　observed　a　significant　increase　in　tumor　burden.　Flow　cytometry　revealed　elevated　MDSCs,　CD8+PD1high+　T　cells,　and　reduced　CD4+　T　cells,　CD8+　T　cells,　and　natural　killer　cells　in　tumors.　Bulk　sequencing　identified　increased　MicroRNA　(miRNA)　hsa-7b-5p　post-splenectomy,　correlating　with　staging　and　immunosuppression.　Similar　results　were　obtained　in　vivo　by　constructing　a　KPC-miRNA　hsa-7b-5p-sh　cell　line.　These　findings　suggest　that　splenectomy　enhances　the　expression　of　miRNA　hsa-7b-5p,　inhibits　the　tumor　immune　microenvironment,　and　promotes　pancreatic　cancer　growth.