Pipeline steel is widely used in various industries, and the sulfur content and inclusions in steel have a significant impact on performance, which determines whether the steel quality is qualified. The experiments were carried out to explore the sulfur content and inclusion evolution of pipeline steel which was deoxidized by Si–Mn–Al with “EAF-LF-VD-T-CC”. The samples of molten steel and slag were taken during the process of LF-VD-Tundish after EAF tapping. The kinetics model was established to simulate the desulfuration process of molten steel in actual production, obtaining a result which the error is within 3 ppm. It can be summarized that proper calcium treatment can transform the inclusion into a liquid inclusion, the value of [Ca] ranges from 25 to 45 ppm. Too high and lower calcium treatment can cause the compositions of inclusions to deviate from the liquid phase area, while too low calcium treatment will increase the overall size and density of the inclusions. In addition, the evolution of inclusion in steel at refining temperature and during solidification process was comprehensively calculated, considering all types of inclusions such as calcium oxide, magnesium oxide, aluminum oxide, calcium sulfide, spinel, calcium aluminate and liquid inclusion. The thermodynamic calculations are in good agreement with experimental results, which can predict the formation of the inclusions in Si–Mn–Al deoxidized pipeline steel.