A field study was undertaken to investigate the complex fouling in an industrial reverse osmosis (RO) desalination plant. Major methods included visual observation, scanning electron microscopy (SEM), energy dispersive X-ray (EDX), Fourier transform infrared spectroscopy (FTIR), and chromatography mass spectrometry (GC/MS), It was found that complex foulants consisted of particulate matter, colloids (Si-Al-Fe), hydrophobic organics (phthalic acid esters) and microorganisms. Adsorption of colloids and organics was believed to be the most crucial factor accelerating the further development of fouling. A preferential cleaning principle of essential foulants (PCPEF) was suggested by the authors and applied successfully in the cleaning-in-place (CIP) process. The preferential order of essential foulants is as follows: silica colloids > adsorbed organic compounds > particulate matter (iron and aluminum colloids) > microorganisms > metallic oxides. The PCPEF requires that if only the essential foulants are eliminated, the subsidiary and/or chelate foulants are cleared away simultaneously or easily by the subsequent cleaning process.