Surface-enhanced Raman scattering has a high sensitivity in the detections of complex biological systems, and it has a lot of potential applications in food inspection, biological imaging and biosensors in biochemistry, etc. Here, we investigate the surface Raman enhancements on gold films of different morphologies and further simulate the enhancements by using the finite difference time domain. To prepare the substrates with different morphologies, polymethyl methacrylate (PMMA) is spin coated 2000 rpm in one minute on a silicon wafer, followed by annealing at 180℃ for 5 min. Then, PMMA is etched by a 20 kV electron beam lithography. With the PMMA used as a soft imprint template, polydimethylsiloxane (PDMS) is dropped on the template then removed gently from the template after drying at 60℃ for 4 h. Finally, a gold thin film is prepared on the PDMS by magnetron sputtering with a current of 10 mA for 15 min. We design two kinds of morphologies:a four-way grid and a square morphology. The dimension of the four-way grids is 40 m and the grid width is 4 upm. The dimension of the square is also 4 upm. The cystine and melamine solutions with concentrations of 50, 100, 200 and 400 ppm are deposited on the surfaces of the gold thin film, respectively. The Raman spectra of cystine and melamine solutions are measured on the substrates with four-way grids and dot arrays. The Raman spectra of cystine on two kinds of substrates show no obvious difference. Due to the relatively small enhancement of melamine, the Raman peaks of melamine solutions of concentrations 50 and 100 ppm on the substrate of square morphologies are not easy to detect. On the contrary, all of the Raman spectra of melamine on the substrate of four-way grid morphologies are clear. The result indicates that the substrate with four-way grids has better sensitivity and enhancement performance. To verify the influence of the morphologies of the substrates on surface Raman enhancement and understand the mechanism of the enhancement, we simulate the scattering spectra and field distributions of different morphologies on gold thin films by using the finite difference time domain method. It is indicated that more complex the structure, the more obvious the enhanced Raman spectra will be. The calculations show that the enhancements of four-way grid morphologies are better than those of square morphologies. The predicted results of the surface enhanced Raman scattering are consistent with the measurements. These results will provide guidance and theoretical basis for further applications of surface enhanced.