Objective To study the significances and expressions of Y14 and Upf1 in human breast cancer tissues and human normal breast tissues. Methods The expressions of Y14 and Upf1 were determined in human breast cancer tissues and human normal breast tissues by immunohistochemistry and laser scanning confocal microscope. Results ①Y14 and Upf1 levels of human breast cancer tissues were obviously higher than those of human normal breast tissues (Plt;0.05). ②Y14 and Upf1 levels of the class Ⅲ were obviously higher than those of the class Ⅰ and Ⅱ in breast cancer tissues (Plt;0.05). ③Y14 and Upf1 levels in breast cancer tissues of patients with positive axillary lymph nodes were obviously higher than those with negative axillary lymph nodes (Plt;0.05). Conclusion The function of nonsense-mediated mRNA decay (NMD) is obviously enhanced in breast cancer tissues. Expressions of Y14 and Upf1 levels of the class Ⅲ cancer tissue and cancer with positive axillary lymph node are high because of NMD.