This research attempts to elucidate the effect of humic acid (HA) on TiO₂ nanoparticle ultrafiltration (UF) membrane fouling, and quantitatively analyze the synergistic membrane fouling mechanisms using interaction energies. The extended Derjaguin-Landau-Verwey-Overbeek (xDLVO) theory was employed to analyze the interaction energies and predict UF membrane fouling. Membrane fouling effects were studied during the dead-end filtration of individual TiO₂ and HA-TiO₂ mixtures using two kinds of polymeric UF membranes. It was found that HA-TiO₂ mixtures lead to greater flux declines than individual TiO₂. For specific foulant, the hydrophobic PVDF membrane showed relative severe membrane fouling than hydrophilic PES membrane. As for the HA-TiO₂ mixture, much higher irreversible fouling was observed compared with that of individual TiO₂. Moreover, this study highlights the importance of HA concentration in synergistic fouling effects of the HA-TiO₂ mixture. The increase of HA concentration caused an increase of contact angle and lower interaction energy, thus aggravating membrane fouling. Results illustrated that synergistic membrane fouling by TiO₂ and HA could be successfully explained using the xDLVO analysis. The extent of membrane fouling turned out to be dominated by Lewis acid-base interaction.