The　fundamental　aspects　of　site　preference　of　alloying　elements　on　sublattice　of　the　strengthen　γ′　phase　with　L12　structure　have　not　been　well　understood,　which　hinders　the　optimized　design　of　advanced　Ni-based　high-temperature　alloys.　In　this　contribution,　the　temperature-　and　composition-dependent　site　occupying　preferences　of　the　binary,　ternary,　and　quaternary　of　Ni3Al-based　γ′　phase　alloyed　with　Mi　where　Mi　represents　the　additional　transitional　metals　Co,　Cr,　Cu,　Fe,　Mn,　Mo,　Re,　Ta,　Ti,　V,　or　W　atoms　(arranged　in　alphabetical　order)　chosen　frequently,　were　studied　using　a　two-sublattice　thermodynamic　model　(Ni,　Al,　Mi)1a(Ni,　Al,　Mi)3c.　The　site　occupying　fractions　(SOFs)　were　calculated　based　on　a　thermodynamic　database　established　in　this　work,　where　the　thermodynamic　data　of　the　end-members　involved　were　obtained　using　first-principles　calculations　and　phonon　spectrum　calculations.　The　calculated　SOFs　results　show　that　there　is　an　obvious　site　preference　for　stoichiometry　binary　Ni3Al,　and　its　site　configuration　changes　from　(Al)1a(Ni)3c　at　room　temperature　to　(Al0.9984Ni0.0015)1a　(Al0Ni0.9994)3c　at　1273　K.　For　the　γ′　phase　with　the　composition　78Ni-26Al-4Mi　(atom　ratio　and　xNi/xAl　=　3:1),　Mo　atoms　always　preferred　to　occupy　the　1a　sublattice　(Al　site),　Co,　Mn,　and　Ti　atoms　always　prefer　the　3c　sublattice　(Ni　site)　in　the　whole　temperature　range,　while　the　site　preference　of　Cr,　Cu,　Fe,　Re,　Ta,　V,　or　W　atom　is　affected　by　temperature.　For　example,　when　the　heat　treatment　temperature　is　lower　than　700　K,　Cr,　Cu,　Fe,　Ta,　V,　and　W　atoms　occupy　the　1a　and　3c　sublattice　randomly,　and　Re　atoms　prefer　to　3c　sublattice,　while　when　the　heat　treatment　temperature　is　higher　than　1273　K,　Cr,　Cu,　and　W　atoms　prefer　3c　sublattice,　Fe　and　Ta　atoms　prefer　to　1a　sublattice,　while　all　Re　atoms　occupy　the　3c　sublattice　exclusively,　and　all　V　atoms　occupy　the　1a　sublattice　exclusively,　respectively.　Likewise,　the　site　preference　of　the　quaternary　system　with　selective　compositions　78Ni-26Al-2　M1-2　M2　was　also　predicted.　Based　on　calculated　SOFs　results,　the　mechanical　and　thermodynamic　properties　were　studied　at　the　ground　state.　It　has　been　revealed　that　Cr,　Re,　and　V　doping　can　improve　the　microhardness　of　Ni3Al　alloys;　in　particular,　the　effect　of　Cr　is　extraordinary;　and　all　elements,　except　Mn,　Mo,　and　Ti,　would　enhance　the　bulk　modulus　of　Ni3Al-based　γ′　phase,　in　which　Mn　have　the　greatest　influence　on　reducing　the　bulk　and　shear　modulus,　respectively.　Furthermore,　all　the　B/G　ratios　of　the　computed　Ni3Al-based　γ′　phase　are　＞1.75,　showing　inherent　ductility.　Only　Cr　doping　significantly　enhances　the　Debye　temperature　of　the　Ni3Al-based　γ′　phase.　©　2022　The　Author(s)