Inclusions and MA islands in X80 pipeline steel were observed and their statistical size characters were obtained by scanning electron microscopy and transmission electron microscopy. The mechanism of microvoid nucleation in X80 pipeline steel was studied through a series of tensile tests with different necking degrees. Microvoid nucleation firstly occurs around calcium treatment inclusions at the early necking stage, while at the deep necking stage, microvoids nucleate by decohesion of MA island/matrix interfaces. Finally the tensile process was analyzed, the curves of true stress to true strain of X80 samples were determined, and the strengths of calcium treatment inclusion/matrix interfaces and MA island/matrix interfaces were calculated by the finite element method.