Seawater-based pretreatment of lignocellulosic biomass is an innovative process at research stage. With respect to process optimization, factors affecting seawater-based pretreatment of lignocellulosic date palm residues were studied for the first time in this paper. Pretreatment temperature (180 degrees C-210 degrees C), salinity of seawater (0 ppt-50 ppt), and catalysts (H2SO4, Na2CO3, and NaOH) were investigated. The results showed that pretreatment temperature exerted the largest influence on seawater-based pretreatment in terms of the enzymatic digestibility and fermentability of pretreated solids, and the inhibition of pretreatment liquids to Saccharomyces cerevisiae. Salinity showed the least impact to seawater-based pretreatment, which widens the application spectrum of saline water sources such as brines discharged in desalination plant. Sulfuric acid was the most effective catalyst for seawater-based pretreatment compared with Na2CO3 and NaOH.