Silane coupling agents containing different specific functionalities are studied to gain understanding of their roles in silica-filled natural rubber (NR) compounds. Five different silane coupling agents, that is bis-(triethoxysilylpropyl) tetrasulfide (TESPT), bis-(triethoxysilylpropyl) disulfide (TESPD), octyltriethoxysilane, vinyltrimethoxysilane, and bis-(trimethyl-silylmethyl) tetrasulfide (TMSMT), are comparatively investigated, by taking the most commonly used TESPT as a reference. The results reveal that alkoxy-based silanes can effectively reduce the filler-filler interaction and lower compound viscosity owing to the effect of silane-to-silica hydrophobation which contributes to better compatibility between silica and NR. The alkoxy-silanes with a sulfur moiety, that is TESPT and TESPD, show more pronounced improvement in overall properties as a result of filler-rubber interactions. The use of TMSMT which has no alkoxy groups but contains only a sulfur moiety elucidates that there are three reaction mechanisms involved in systems with sulfur-alkoxy-based silane. These are as follows: (1) the silane-to-silica or silanization/hydrophobation reaction; (2) the silane-to-rubber or coupling reaction; and (3) rubber-rubber crosslinking originating from active sulfur released by the polysulfide-based silane TESPT. These simultaneous reactions are temperature dependent, and show an optimum level at a dump temperature of approximately 140-150°C, as depicted by filler-filler and filler-rubber interactions, as well as mechanical properties of such compounds.