Intermediate-depth earthquakes in cold subduction zones are observed within the subducting oceanic crust, as well as the mantle(1,2). In contrast, intermediate-depth earthquakes in hot subduction zones predominantly occur just below the Mohorovicic discontinuity(1). These observations have stimulated interest in relationships between blueschist-facies metamorphism and seismicity, particularly through dehydration reactions involving the mineral lawsonite(1,2). Here we conducted deformation experiments on lawsonite, while monitoring acoustic emissions, in a Griggs-type deformation apparatus. The temperature was increased above the thermal stability of lawsonite, while the sample was deforming, to test whether the lawsonite dehydration reaction induces unstable fault slip. In contrast to similar tests on antigorite, unstable fault slip (that is, stick-slip) occurred during dehydration reactions in the lawsonite and acoustic emission signals were continuously observed. Microstructural observations indicate that strain is highly localized along the fault (R-1 and B shears), and that the fault surface develops slickensides (very smooth fault surfaces polished by frictional sliding). The unloading slope during the unstable slip follows the stiffness of the apparatus at all experimental conditions, regardless of the strain rate and temperature ramping rate. A thermomechanical scaling factor(3) for the experiments is within the range estimated for natural subduction zones, indicating the potential for unstable frictional sliding within natural lawsonite layers.