The strong metal–support interaction (MSI) has been widely attributed to enhanced catalytic activity. However, this attribution might be wrong in catalytic ozonation, since MSI that is too strong might impede the activation of electron-poor ozone molecules. Herein, we reported a strategy to subtly modulate the Mn–O–Si interaction by intercalating the carbon film between the silica support and active manganese oxide. When using MnOx/0.5C/SiO2 with the moderate MSI as a catalyst in the catalytic ozonation of refractory paracetamol (PCM), 91.1 ± 2.4% of PCM was removed within 30 min, about 30% higher than that using the catalyst of MnOx/SiO2 with a strong MSI. Moreover, the reaction rate reached 8.01 × 10–2 min–1, 2.2 and 1.3 times that with MnOx/SiO2 and MnOx/1C/SiO2, respectively. Importantly, further integration of MnOx/0.5C/SiO2 into membrane filtration achieved high rejections of PCM (>94.3%) under various realistic water scenarios during a continuous 12 h operation, demonstrating strong resistance to environmental matrices interference. Experimental and theoretical evidence revealed that the moderate MSI resulted in the high dispersion of active MnOx nanoclusters in the size of 2.3–4.4 nm and promoted the adsorption of ozone over MnOx and its dissociation into surface *O, •OH, •O2–, and 1O2 for decontamination. As a constructive work, this study revealed the significance of MSI in catalytic ozonation and offered a simple regulation method for constructing active interfaces of metal-supported catalysts.