Paracetamol　(PAR)　has　received　increasing　concern　due　to　its　large　usage,　ubiquitous　detection　in　environment　and　high　ecotoxicology　risk.　This　study　investigated　the　effect　of　PAR　on　the　growth　and　lipid　production　of　Coccomyxa　subellipsoidea,　removal　of　PAR　by　C.　subellipsoidea,　and　the　metabolic　difference　in　C.　subellipsoidea　after　exposure　to　PAR.　The　PAR　promoted　C.　subellipsoidea　growth　but　the　biomass　increment　reduced　with　PAR　concentration　increasing.　Acclimation　evolution　could　enhance　removal　capacity　of　C.　subellipsoidea　to　PAR.　Compared　to　wild　C.　subellipsoidea,　the　removal　percentage　of　PAR　by　acclimated　C.　subellipsoidea　increased　2.71-fold,　the　content　and　yield　of　lipid　as　well　as　the　content　of　unsaturated　fatty　acid　in　acclimated　C.　subellipsoidea　significantly　increased　by　1.06-,　1.13-　and　1.12-fold,　respectively.　The　metabolism　fate　of　PAR　analysis　revealed　that　p-aminophenol　was　the　first　step　degradadation　product,　and　the　molecular　docking　simulating　suggested　p-aminophenol　was　the　most　prone　to　undergo　metabolism.　Differential　metabolites　analysis　showed　that　the　up-regulating　glutathione　with　2.20-fold　in　C.　subellipsoidea　withstanded　oxidative　stress　from　PAR　and　actuated　the　PAR　degradation,　the　up-regulating　citric　acid　and　fumarate　as　well　as　malate　used　as　precursor　of　lipid　biosynthesis　actuated　lipid　accumulation.　This　work　provides　new　insights　for　using　microalgae　for　efficient　treatment　of　wastewater　containing　pharmaceuticals　contaminants　(PCs)　coupling　high　value-added　products　production.　©　2023　Elsevier　B.V.