Breast cancer has become one of the leading cause of women’s death around the world. Breast cancer can be caused by genetic or environmental factors. Human epidermal growth factor receptor 2 (HER2) is one of the main causes of breast cancer. The HER2 tyrosine kinase plays a significant role in the dimerization reaction which causes auto-phosphorylation of tyrosine residues in the cytoplasmic domain that triggers the growth of the cancer cells. Inhibition of HER2 protein activity can be a potential alternative for breast cancer treatment. Flavonoids have become an important scaffold in medicinal chemistry due to its bioactivity and availability. Therefore, flavonoids were used as the database on this in silico research. Fragment-based drug design was applied to determine novel drug candidates. Three potential candidates were obtained in this research. VC-255 was selected as the best inhibitor candidates for HER2 tyrosine kinase.