Background:　FAM110A　belongs　to　the　FAM110　family,　which　mainly　functions　in　biological　processes　associated　with　the　cell　cycle.　However,　the　biological　functions　in　which　FAM110A　participates　are　largely　undefined.　In　particular,　its　potential　role　in　cancer　remains　unknown.　The　goal　of　this　study　was　to　uncover　the　role　and　mechanism　of　FAM110A　in　pancreatic　cancer.　Methods:　Based　on　bioinformatics　databases,　qPCR　and　Western　blot　assays,　we　verified　the　elevated　expression　level　of　FAM110A　in　PDAC.　Subsequently,　FAM110A,　HIST1H2BK　and　TSPAN1　overexpression　or　knockdown　stable　transfected　cells　were　employed　for　biological　functions＇　studies　to　explore　the　role　in　PDAC　in　vitro　and　in　vivo.　RNA-Seq,　Western　blot　and　luciferase-reporter　assays　were　used　to　explore　mechanism　of　FAM110A　action　in　PDAC,　and　the　involved　pathway　was　verified　by　tumor　phenotypic　rescue　experiments.　Results:　In　this　study,　we　demonstrated　for　the　first　time　that　FAM110A　is　an　oncogene　that　promotes　cell　proliferation,　migration,　invasion　and　tumorigenesis　in　pancreatic　cancer.　HIST1H2BK　was　identified　as　the　downstream　target　of　FAM110A,　while　the　promotion　effect　caused　by　FAM110A　overexpression　could　be　abolished　by　HIST1H2BK　knockdown.　Moreover,　for　the　first　time,　we　revealed　the　oncogenic　role　of　HIST1H2BK　in　pancreatic　cancer,　and　the　tumor-promoting　capacity　of　HIST1H2BK　may　be　associated　with　its　regulatory　effect　on　G9a.　In　addition,　we　demonstrated　that　TSPAN1　displayed　a　positive　transcriptional　regulatory　effect　on　FAM110A.　Conclusions:　Collectively,　FAM110A　plays　an　oncogenic　role　in　PDAC,　and　the　newly　identified　TSPAN1/FAM110A/HIST1H2BK/G9a　pathway　is　involved　in　the　modulation　of　pancreatic　cancer　progression　and　provides　a　novel　prognostic　and　therapeutic　strategy　for　pancreatic　cancer　treatment.