Friction stir welding (FSW) is a solid-state joining process which employs a lower joining temperature than that used in fusion welding. In this study, the weldability and the effects on the interfacial microstructure of alloying elements in dissimilar metal lap joints between commercial pure titanium and nickel-based alloy (Inconel 625) were examined by friction stir welding. The thickness of the stir zone on the titanium side decreased with increasing tool rotation speed. At high rotation speeds, the titanium adhered to the surface of the FSW tool's shoulder and probe. Fracture occurred in the region in the stir zone of titanium where its thickness decreased by tensile share test. A thin reaction layer was formed at the joint interface under suitable joining conditions. Transmission electron microscopy revealed two types of layers in this reaction layer. The layer on the titanium side was less than 100 nm thick and contained nickel, titanium and a small amount of iron; the other layer, on the Inconel 625 side, was less than 50 nm thick and contained all the alloying elements in Inconel 625, plus titanium. A quantitative analysis of the titanium-side layer using TEM-EDX showed its composition to be 68.9% Ti and 29.2% Ni (by atomic percentage), suggesting that the layer is comprised of the intermetallic compound Ti₂Ni.