This study explores the development of 4,5,6,7 tetrahydrobenzo[b]thiophene derivatives as potential EGFR inhibitors with anticancer activity. Molecular docking identified three key compounds—PI 13, PI 40, and PI 5—with strong binding affinities, influenced by electron-withdrawing groups like hydroxyl groups on the aromatic ring. These compounds were synthesized and tested for anticancer efficacy using the MTT assay on MCF-7 cells. PI 13 showed the highest potency (IC50 = 0.062 μM), with PI 40 and PI 5 also demonstrating significant activity. The results confirm a strong correlation between docking predictions and biological activity, supporting their potential as targeted anticancer agents.