Aiming at the frequent issue of pit-shaped surface defects in S-bearing and Al-killed steel products and the related poor castability due to submerged entry nozzle (SEN) clogging, the melting and casting process of a popular auto steel Cf53 has been studied based on in-situ investigation and experimental analysis. To clarify the generation of the pit-shaped defects, the local surface chemistry, evolution of steel inclusions throughout the melting process, SEN clogging substances, and the internal relationship among them were systematically analyzed. The results show that this type of defect in the Cf53 rolled products is caused by the large-sized composite inclusions rich in CaS, which originate from the molten steel during the refining process, gradually accumulate on the inner wall of the SEN during casting, and finally lead to SEN clogging. The loose structure of clogging inclusions makes them prone to fall off into the mold and get trapped by solidifying steel shell. The formation mechanism of the inclusions was studied through FactSage software calculation. The results show that the increase in total sulfur and total calcium content, and the decrease in total oxygen content and temperature in steel will lead to CaS inclusion formation, which agrees reasonably well with experimental results. An optimized refining process to reduce calcium addition into molten steel is proposed accordingly, which achieves a remarkably alleviation in casting SEN clogging and an elimination of the pit-shaped defects on the final rolled products as well.