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Abstract This work was designed to compare the effectiveness of in-situ coagulation and MIEX as pre-treatments prior to ultrafiltration (UF) to improve organic matter (OM) removal and mitigate membrane fouling. Three kinds of OMs, i.e. salicylic acid (SA), humic acid (HA) and bovine serum albumin (BSA) were employed. The experimental results show that coagulation-UF led to most effective removal of HA (almost 90%), while the SA was uncoagulated and least removable, with the rejection rate of about 55%. Conversely, MIEX present superior ability for removing SA, contributing to additional efficiency of 71.95–77.21% than UF alone. Proper dosage of Al-based coagulants could alleviate flux loss, especially in the cases of HA and BSA. Increasing coagulant dose resulted in continuous decrement of irreversible resistance (R ir), which dominated the membrane fouling development by the SA water. For HA and BSA waters, alternatively, variations of R r determined the flux declines. Floc compact degree was the decisive factor for R r for coagulated SA; while for HA and BSA, R r was most related to the floc size and foulant-foulant interaction. MIEX was most effective for alleviating flux loss when treating the hydrophilic SA with small molecules and for all the cases, MIEX exerted little influence on the R r values. Graphical abstract Schematic diagram of the coagulation/MIEX-ultrafiltration hybrid test setup. Image 1 Highlights • Coagulation improved removal rate and UF flux more significantly for HA and BSA. • MIEX is preferable to coagulation combined with UF when treating hydrophilic SA. • R r and R ir determined UF fluxes by coagulated HA/BSA and SA, respectively. • Coagulation reduced R ir by promoting floc growth and restraining pore blockage. • MIEX imposed slighter effect on particle size and fouling resistance. [ABSTRACT FROM AUTHOR]