26 sets of molecular compounds were studied for anti-esophageal cancer activity. B3LYP/6-31+G* basis set was used for Quantum chemical calculation and the obtained molecular descriptors were used for QSAR studies via Gretl software. Thus, the developed model predicted efficiently and it was used to predict the cytotoxicity of the proposed compounds. Furthermore, molecular docking study was carried out on esophageal cancer cell line (2leo) and it was observed that A13 inhibited more than all the studied compounds. Also, all the studied compounds were more effective than the standard (5-FU).