The crystal structure consists of a network of guanidinium cations and chloride anions linked by N–H···Cl hydrogen bonds.

However, some stronger bases can deprotonate it, such as sodium hydroxide: The equilibrium is not complete because the acidity difference between guanidinium and water is not large.

This is the result of inhibition of the Hsp104 chaperone protein known to play an important role in prion fiber fragmentation and propagation.

Greenstein (1938, 1939), however, appears to be the first to discover the high denaturing action of guanidinium halides and thiocyanates in following the liberation of sulfhydryl groups in ovalbumin and other proteins as a function of salt concentration.

[6] Guanidine hydrochloride is indicated for the reduction of the symptoms of muscle weakness and easy fatigability associated with Eaton-Lambert syndrome.