Cancer remains a global health challenge, encompassing over 200 distinct types typically classified by the specific tissues where abnormal cell growth originates. As one of the leading causes of mortality in the 21st century, cancer significantly hinders the increase of global life expectancy. The diversity and complexity of cancer types highlight the urgent need for ongoing research, prevention strategies, and improved treatment options to mitigate its global impact. In the search for new potential drug candidates acting as anticancer agents, numerous synthetic and natural compounds have been developed and tested against various cancer cells. Among these natural compounds, Arylnaphthalene lignan lactones have attracted our interest. These compounds are found in various plant species such as Phyllanthus and Cleistanthus, and exhibit a range of biological activities, including antioxidant, anti-inflammatory and anticancer properties. Arylnaphthalene lignan lactones were subjected to an in silico study to investigate their potential to act against colon cancer by inhibiting a tyrosine kinase, the Epidermal Growth Factor Receptor (EGFR). A docking simulation was performed in the active pocket of the human EGFR complexed with 4-Anilinoquinazoline (PDB: 1M17). The studied derivatives showed excellent stability inside the active site, with estimated docking scores of -8.02 and -7.96 kcal/mol. Additionally, significant interactions similar to those formed by 4-Anilinoquinazoline were present in the studied compounds, including hydrogen bonds with Met769 as well as hydrophobic contacts with residues in the EGFR cavity. Furthermore, ADMET analysis was performed to verify their pharmacokinetic properties and toxicity.