Follow the E17 direction Gent. After 20 kilometers, turn right at the Sint-Niklaas exit. The first exit will take you to the city centre. Follow the 'P-route' to find a parking space.
Sint-Niklaas is also accessible via the E34. You then take exit Vrasene and reach the north side of the city via the N451 which runs through one of the city's municipality's, Nieuwkerken.