First results on femtosecond laser 3D-microstructuring are reported in a novel class of organic-inorganic hybrid materials based on titanium oxide gels. Transparent optical-grade polished hybrid samples demonstrate strong photosensitivity assigned to electrons trapped as Ti3+ centers. Two different regimes of the microstructuring are observed: reversible and irreversible. In tight-focusing conditions using “on-the-fly” technique the single-pulse microstructuring is achieved with nanojoule laser pulses. The process thresholds have been studied on the surface and into the bulk of the material with irradiation by 1, 2, 10, and 100 laser pulses. A reduction of the damage threshold fluence by a factor of 2.5 is observed when increasing exposure from 1 pulse (1.2 J/cm2) to 100 pulses (0.5 J/cm2).