We report on the modification of the wettability of stainless steel by picosecond laser surface microstructuring in this paper. Compared with traditional methods, picosecond laser-induced surface modification provides a fast and facile method for surface modification without chemical damage and environmental pollution. As a result of treatment by 100 ps laser pulses, microstructures are fabricated on the stainless steel sample surface, contributing to the increase of the contact angle from 88° to 105°, which realizes a transformation from hydrophilicity to hydrophobicity. The morphological features of fabricated microstructures are characterized by scanning electron microscopy and optical microscopy.