A method of manufacturing a semiconductor structure. A patterned first hard mask is formed on a substrate. The patterned first hard mask includes first trench patterns extending along a first direction. A second hard mask is then formed on the patterned first hard mask. A patterned photoresist layer is formed on the second hard mask. The patterned photoresist layer includes second trench patterns extending along a second direction. The second trench patterns intersect first trench patterns. Using the patterned photoresist layer as an etch mask, a first etch process is performed to transfer the second trench patterns into the patterned first hard mask and the second hard mask. Subsequently, using the patterned first hard mask as an etch mask, a second etch process is performed to transfer the first trench patterns and the second trench patterns into the substrate.