This　study　provides　novel　insights　into　the　interactions　among　humic　acid　(HA),　calcium　ion　(Ca2+),　and　nanofiltration　membranes,　revealing　their　critical　impact　on　rejecting　nine　antibiotics　and　six　estrogens,　common　environmental　pollutants.　In　the　presence　of　HA,　the　normalized　water　flux　of　NF270　and　NF90　was　decreased　to　92%　and　89%,　respectively,　and　was　further　reduced　to　71%-83%　and　74%-79%　with　the　addition　of　Ca2+,　resulting　from　the　reduced　hydrophilicity　by　HA-Ca-induced　deposition.　HA　reduced　antibiotic　rejection　by　27%　for　NF270　and　3%　for　NF90,　attributed　to　weakened　charge　repulsion　and　size　exclusion　(reflected　by　decreased　membrane　surface　charge　and　boron　rejection).　Adding　Ca2+　further　decreased　antibiotic　rejection　by　up　to　48%　for　NF270　and　6%　for　NF90,　as　charge　repulsion　and　size　exclusion　were　further　diminished.　HA　also　decreased　estrogen　rejection　by　8%-16%　for　NF270　and　5%-14%　for　NF90,　due　to　weakened　size　exclusion.　After　adding　Ca2+,　estrogen　rejection　showed　inconsistent　trends　due　to　competing　effects　of　size　exclusion　and　hydrophobic　interaction.　Therefore,　size　exclusion　and　charge　repulsion　are　the　main　rejection　mechanisms　for　the　negatively　charged　antibiotics,　however,　size　exclusion　and　hydrophobic　interaction　are　for　the　neutral　and　hydrophobic　estrogens.　The　reduced　membrane　permeability　and　selectivity　highlight　the　importance　of　effectively　managing　organic　matter　and　divalent　cations　in　feedwater　to　ensure　both　treatment　efficiency　and　long-term　membrane　stability.　©　2025　Elsevier　B.V.