A novel approach to region location of serial numbers in Optical Character Recognition (OCR) of RMB is proposed. Firstly, a binary image was obtained by applying fixed threshold segmentation to the banknote image. Secondly, some of sample points of left and lower edges were selected by using sequential scanning. Thirdly, due to the characteristic that the dot-product of vectors from two edge lines on non-damaged areas is zero, the sample points of edges on non-damaged areas were sifted by filtering sample points on damaged areas. So, a slope angle and a lower-left corner can be got by using least-square line regression on these points. Finally, the image was rotated and the lower-left corner after correction was gained by using rotation formula. Meanwhile, the number region was located by shifting fixed distance from anchor point, which makes the time consumption limited to few microseconds. The experimental results prove good robustness and high time efficiency, so the scheme has a broad application prospects in the system of optical character recognition of banknote.