The　aim　of　this　research　is　to　investigate　the　influence　of　key　parameters　of　variable　gradient　drilling　by　injecting　hollow-glass　spheres　(Referred　to　as　HGS,　it　is　a　low-density　and　micron-sized　hollow　glass　sphere)　on　the　interphase　mass　transfer　rate　of　the　surface　boundary　layer　of　the　sliding　bubble　in　the　annulus　and　the　flow　law　of　the　two-phase　flow　in　the　wellbore　after　the　gas　intrusion　occurred.　Firstly,　the　key　parameters　of　variable-gradient　drilling,　such　as　HGS　volume　fraction,　HGS　density,　the　depth　of　the　filter　separator,　were　coupled　with　the　model　of　non-equilibrium　interphase　mass　transfer　rate　and　the　mathematical　model　of　two-phase　flow　to　establish　a　new　two-phase　flow　model　of　transient　non-equilibrium　interphase　mass　transfer　for　variable-gradient　drilling.　Secondly,　the　existing　classic　model　and　measured　data　were　used　for　comparative　analysis　with　the　model　in　this　paper,　and　then　the　accuracy　of　the　model　in　this　paper　was　verified.　Thirdly,　based　on　the　on-site　data,　the　numerical　calculations　and　sensitivity　analysis　were　carried　out　using　the　model　in　this　paper.　Finally,　a　comparative　analysis　of　the　interphase　mass　transfer　rate　was　performed　under　equilibrium　and　non-equilibrium　conditions.　In　addition,　the　influence　on　non-equilibrium　interphase　mass　transfer　rate　of　surface　boundary　layer　of　the　bubble,　bottom　hole　pressure,　overflow　rate　and　overflow　rate　exerted　by　different　separator　positions,　HGS　volume　fraction,　HGS　density,　and　pumping　rate　was　studied.　The　results　indicated　that　the　interphase　mass　transfer　rate　under　the　non-equilibrium　condition　was　lower　than　that　under　the　equilibrium　condition　when　the　both　were　at　the　same　well　depth　or　at　the　same　circulation　time.　The　interphase　mass　transfer　rate　enhanced　with　the　increase　of　pumping　rate,　the　depth　of　filter　separator　and　HGS　density,　but　decreased　with　the　increase　of　HGS　volume　fraction.　The　bottom-hole　pressure　was　negatively　correlated　with　the　depth　of　the　filter　separator　and　the　volume　fraction　of　HGS,　on　the　contrary,　it　was　positively　correlated　with　the　HGS　density.　Similarly,　the　gas　void　fraction,　overflow　rate　and　overflow　were　positively　correlated　with　the　depth　of　filter　separator　and　HGS　volume　fraction,　but　negatively　correlated　with　the　HGS　density.　This　research　can　provide　a　certain　theoretical　reference　for　variable　gradient　drilling.