In order to investigate the modification behavior and regularity of inclusions in X80 pipeline steel by Mg-treatment, the comparative industrial experiments of Mg-treatment and Ca-treatment in X80 pipeline steel were carried out. Mg and Ca were added to the steel in the form of cored wire after RH (Ruhrstahl-Hereaeus vacuum degassing) process. After adding Ca-containing cored wire, the inclusions were transformed into CaO–Al2O3 in the steel. With the progress of smelting, the cleanliness of molten steel became worse, and the equivalent diameter of inclusions was at a higher level. Mg-treatment had a good effect on the modification of inclusions. After Mg-containing cored wire was added to the steel, Al2O3 and CaO–Al2O3 in the steel were transformed into MgO, MgO·Al2O3, and CaO–MgO–Al2O3 inclusions, which were basically spherical. The initial precipitated MgO became the core of other inclusions in the steel, which promotes the precipitation of MgO·Al2O3. After Mg-treatment, almost no unmodified calcium aluminate inclusions existed in the hot rolled plate, and the cleanliness of the steel was improved. The effect of Ca and Mg on the transformation of inclusions in pipeline steel was studied by thermodynamic calculation, the result of which is consistent with the experimental results.