Particles were the most frequent foulants in seawater reverse osmosis (SWRO) desalination. In this study, the fouling characteristic of particles in a large scale SWRO desalination plant from northern China was analyzed systematically by multiple methods. The particle fouling pattern, particle size distribution (PSD), and mineralogical composition were investigated by optical microscopy, scanning electron microscopy with energy dispersive spectrometer, laser diffraction particle size analyzer, X-ray diffraction, and wavelength dispersive X-ray fluorescence spectrometer. Chemical analysis indicated that Na, Mg, Si, and Al were the predominant elements contributing to the fouling particles. The particle deposition had a very broad PSD including ultrafine particles, fine particles, and medium particles due to the failure of the ultrafiltration (UF) system. The mineralogical components were quartz, muscovite, talc, albite, microcline, clinochlore, hematite, and amphibole in descending order. Finally, the long immersing experiment shows that 2.5% hydrofluoric acid processing could eliminate the particles effectively and improve the water flux of the fouled membrane obviously. On the basis of the above results, an in-depth understanding and mitigation of the particles fouling behavior during SWRO desalination would be put forward.