Cold　atmospheric　plasma　(CAP)　has　shown　strong　anti-cancer　capability　in　vitro　and　in　vivo.　The　interaction　between　CAP　and　cancer　cells　build　the　foundation　to　understand　the　anticancer　effect　of　a　direct　CAP　treatment.　The　CAP-based　activation　phenomenon　is　a　key　factor　to　understand　the　CAP　cancer　treatment.　The　CAP-treated　pancreatic　adenocarcinoma　cells　instantaneously　entered　a　specific　activation　state,　in　which　these　cancer　cells　become　very　sensitive　to　the　cytotoxicity　of　both　reactive　oxygen　species　and　reactive　nitrogen　species.　Here,　we　present　a　roadmap　of　control　the　basic　operational　parameters　of　the　CAP　jet　(the　helium　flow　rate,　the　discharge　voltage,　and　the　discharge　frequency)　on　the　activation.　Among　three　parameters,　the　discharge　voltage　shows　the　largest　impact　on　the　activation　phenomenon.　The　maximum　activation　effect　occurred　when　the　discharge　voltage　reached　a　medium　level.　A　0D　chemical　simulation　revealed　that　such　maximum　activation　effect　may　be　due　to　the　maximum　densities　of　several　short-lived　reactive　species　in　CAP　jet　at　a　certain　level　of　discharge　voltage.