An osmotic dilution process of hybrid forward osmosis (FO) and reverse osmosis (RO) was applied at pilot-scale to integrate wastewater treatment with seawater desalination in a municipal wastewater treatment plant. The aim of this study is to expand the understanding of multiple FO fouling indexes (i.e., MFI-UF and ORI) to not only obtain insight on fouling characteristics of the FO process but also optimize the operation of the osmotic dilution process. The correlation between the fouling indexes and performance of the FO membrane (i.e., transmembrane inlet pressure (TMIP), differential pressure (DP)) was first validated based on the operation data from the seven-month pilot run. MFI-UF was then selected for measuring the fouling potential according to the pretreatment process (or source water), whereas ORI was obtained for optimizing the cleaning protocol of the FO process to support the stable operation of the FO plant. The sensitivity analysis of the seasonal effect verified the correlation between MFI-UF and FO performance. The results of this study are expected to provide practical insight and technical guidelines to FO based plant engineers/operators. Display omitted •Applicability of multiple FO fouling indexes was validated at pilot scale.•Long-term performance was assessed by adopting different pretreatment strategies.•A close relationship between MFI-UF and FO ΔDP was observed.•ORI was able to predict the FO TMIP precisely.•MFI-UF and ORI can be applied as plant–assistance criteria for FO process.