gamma-Valerolactone (GVL) can be used as an efficient and practical alternative to the banned and commonly used dipolar aprotic solvents. In this contribution GVL has been used as a non-toxic, biodegradable, biomass-derived medium, for the definition of a simple and general protocol for the Sonogashira cross-coupling reaction. The chemical efficiency of GVL as medium is excellent and the best results have been obtained using DABCO as base allowing to isolate products 3a-q in 60-96% yields. These results represent an example that proves that biomass-derived safer solvents can be used efficiently in common transformations reaching higher greenness/sutainability as well as high chemical efficiency