Mechanisms for Ssp3–H functionalization of thiolacetic acid, initiated by AIBN, have been investigated by M06‐2X‐D3/ma‐def2‐TZVP method and basis set, and SMD model was employed to simulate the solvent effect of toluene. The computational results suggest that azodiisobutyronitrile (AIBN), as the radical initiator, would have an intramolecular homolytic reaction; then Ssp3–H activation of thiolacetic acid could be finished via two possible paths; the obtained thiyl radical and diyne would go through electrophilic reaction, ring‐closure reaction, and SN2 reaction to yield 3,4‐fused‐ring‐substituted thiophenes. While in the second part, the mechanism of side reaction has also been investigated, revealing that main reaction has a lower energy barrier. Localized orbital locator isosurfaces and electron spin density isosurface graphs can analyze the structures and reveal the substances.