In　the　process　of　deepwater　drilling,　the　control　difficulty　of　wellbore　pressure　is　high　and　downhole　complexities　happen　frequently　under　the　influence　of　sea　water　and　submarine　geological　conditions.　To　solve　the　problem　of　high　control　difficulty　of　wellbore　pressure　during　deepwater　drilling　with　narrow　density　window,　a　new　multi-gradient　managed　pressure　drilling　method　is　proposed　recently,　but　the　influence　laws　of　multi-gradient　control　parameters　on　wellbore　pressure　under　the　gas　invasion　condition　of　multi-gradient　drilling　are　less　researched.　In　this　paper,　a　transient　gas-liquid　two-phase　flow　model　for　deepwater　multi-gradient　drilling　is　firstly　established　by　considering　the　energy　exchange　between　wellbore　and　formation,　the　mass　transfer　between　gas　phase　and　liquid　phase　and　the　comprehensive　influence　of　hollow　glass　sphere　(HGS)　on　fluid　physical　parameter.　Then,　the　model　is　iteratively　solved　by　using　the　implicit　difference　method,　and　the　influence　laws　of　multi-gradient　parameters　on　bottom-hole　pressure　and　cross-section　gas　void　fraction　are　analyzed.　Finally,　the　multi-gradient　control　parameters　are　optimally　designed　according　to　the　principle　of　variation　coefficient　weighting　method,　and　the　optimal　control　method　for　different　control　objectives　is　proposed.　And　the　following　research　results　are　obtained.　First,　compared　with　the　bottom-hole　constant-pressure　managed　pressure　drilling,　adjusting　the　multi-gradient　control　parameters　can　provide　a　higher　response　rate　of　bottom-hole　pressure.　Second,　when　the　maximum　response　rate　of　bottom-hole　pressure　is　taken　as　the　control　target,　adjusting　the　volume　fraction　of　HGS　is　the　best　in　control　effect.　Third,　when　the　minimum　cross-section　gas　void　fraction　of　wellhead　is　taken　as　the　control　target,　adjusting　the　position　of　the　separator　is　the　best　in　control　effect.　In　conclusion,　this　method　provides　a　reference　for　the　optimized　design　of　managed　pressure　drilling　technology　under　a　gas　invasion　condition,　as　well　as　theoretical　guidance　and　technical　support　for　the　safe　drilling　in　deep　waters,　and　its　popularization　and　application　is　conducive　to　the　efficient　development　of　deepsea　oil　and　gas.　©　2022　Natural　Gas　Industry　Journal　Agency.　All　rights　reserved.