The paleothermometer on the base of isoprenoid glycerol dialkyl glycerol tetraethers (iGDGTs) has been widely applied to various marine settings to reconstruct past sea surface temperatures (SSTs). However, it remains uncertain how well this proxy reconstructs SSTs in marginal seas. In this study, we analyze the environmental factors governing distribution of iGDGTs in surface sediments to assess the applicability of paleothermometer in the South China Sea (SCS). Individual iGDGT concentrations increase gradually eastwards. Redundancy analysis based on the relative abundance of an individual iGDGT compound and environmental parameters suggests that water depth is the most influential factor to the distribution of iGDGTs, because thaumarchaeota communities are water-depth dependent. Interestingly, the SST difference (ΔT) between derived temperature and remote-sensing SST is less than 1°C in sediments with water depth>200 m, indicating that was the robust proxy to trace the paleo-SST in the region if water depth is greater than 200 m.