Medium-high carbon steels having a high quality are widely used in China. It is advantageous to produce high value-added hot-rolled plates with the crystal refined and chemical composition homogenized in the casting slabs. However, element segregation occurs easily during high-medium carbon steels’ production. Generally, the centerline segregation is improved by enlarging the equiaxed zone with low-superheat casting and electromagnetic stirring (EMS). Studies were conducted on centerline segregation of S50C steel slabs with a thickness of 52 mm produced by the compact strip production (CSP) process in China without EMS equipped. By sampling along the width at different position, the secondary dendrite arm spacing (SDAS) was measured after etching and picture processing, based on which the cooling rate was calculated. It was found that the cooling rate increased from the center to the surfaces of the slabs ranging in 1~20 K/s, 10 times faster than that of a conventional process. The faster cooling rate led to a refined solidifying structure and columnar dendrite through the center of the slabs. The SDAS tended to increase from surfaces to the center, ranging only 32~120 μm smaller than that of a conventional process in 100~300 μm, indicating a finer solidifying structure by the CSP process. Results by EPMA indicated that elements C, Si, and Mn distribute in dispersed spots, increasing towards the center, and the centerline segregation changed in a narrow range: for C mainly in 1.0~1.1, Si in 0.98~1.08, Mn in 0.96~1.02, respectively, meaning a more chemical homogenization than that of thick slabs. Elements’ segregation originated from solute redistribution between solid and liquid. According to thermodynamic calculation, δ region of S50C is so narrow that the solute redistribution mainly occurred between γ-Fe and liquid during solidification. As the equilibrium partition coefficient of element C was the smallest, it was easy for C to be rejected to the residual liquid in the inter-dendritic space, leading to obvious segregation, relatively. Besides, as a result of high-cooling intensity, the solidifying structure became so fine that the Fourier number increased and the volume of the residual liquid decreased, making centerline segregation alleviated effectively both in volume and degree. Although bulging was observed during the industrial experiment, the centerline segregation was still inhibited obviously as the refining solidifying structure with permeability ranged only in 0.1~2.3 μm2 from the surfaces to centerline, which showed a good resistance on the residual flow towards the centerline.