A method of fabricating a metal silicide layer over a substrate is provided. First, a hard mask layer is formed over a gate formed on a substrate and a portion of the substrate is exposed. Thereafter, a first metal silicide layer, which is a cobalt silicide or a titanium silicide layer, is formed on the exposed substrate. After that, the hard mask layer is removed and a second metal silicide layer is formed over the gate, wherein a material of the second metal silicide layer is selected from a group consisting of nickel silicide, platinum silicide, palladium silicide and nickel alloy. Since different metal silicide layers are formed on the substrate and the gate, the problem of having a high resistance in lines with a narrow line width and the problem of nickel silicide forming spikes and pipelines in the source region and the drain region are improved.