The factors influencing the graphoepitaxy of organic semiconductor α-sexithiophene (6T) on thermally oxidized silicon substrates were studied and it was discovered that a wider pitch in the microgrooves decreased the degree of graphoepitaxy. A more significant finding was that in-plane orientation could be changed by simple surface treatment. On UV∕ozone-treated substrates (hydrophilic condition), the b-axis of 6T was parallel to the grooves. Further surface treatment with hexamethyl-disiloxane (under hydrophobic conditions) changed this in-plane orientation by 90°. This change is due to the interaction between the topmost chemical species (functional groups) of the groove walls and organic molecules, a behavior peculiar to organic graphoepitaxy and exploitable for optimal orientation control in device processing. The nucleation and growth processes that cause the graphoepitaxy are discussed, based on the experimental results.