Introduction Breast cancer is one of the most common types of cancer in women, and 70% of breast cancer is caused by overexpression of the estrogen receptor (ER). ER represents a vital and important pharmaceutical target against cancer. It is targeted by pharmaceutical agents for hormone replacement in menopausal women and in reproductive cancers such as prostate cancer, uterine cancer, and breast cancer [1]. ERs are classified into two types, ER alpha and ER beta which belong to the super family of nuclear receptors. ER alpha and ER beta have similar but not identical structures. Regulation of ER alpha causes cell proliferation, inhibition of apoptosis, stimulation of invasion and metastasis, and promotion of angiogenesis. Although not much is known about ER beta, its function is believed to be distinct from ER alpha and likely to have an opposite activity to tumor growth [2]. Tamoxifen is the regularly prescribed drug for the treatment of breast cancer. The anticancer property of Tamoxifen has been attributed to its antiestrogenic properties. The use of tamoxifen is limited due to acquired resistance to tamoxifen in many cancer patients [3]. Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs that have an anti-inflammatory action and are also used for fever (antipyretics) and for pain relief. Aspirin is the first NSAID used to treat human ailments, and is derived from willow bark. NSAIDs act as non-selective inhibitors of the enzyme cyclooxygenase (COX), causing the reduction of the formation of prostaglandins and thromboxane. NSAIDs have recently received increasing attention as anticancer agents. In vivo studies with NSAIDs have demonstrated the anti-tumor properties of these drugs against the breast. correlate NSAID docking score with human estrogen receptor alpha (PDB ID: 3ERT) and estrogen-related receptor gamma (PDB ID: 2GPU). In the present study, the results show that NSAIDs have good binding energy values ​​with both ER proteins. Valdecoxib, withdrawn from the market, had shown good energy values ​​in optimized NSAIDs. The antagonistic action of NSAIDs towards the ER could be one of the possible reasons why NSAIDs have anticancer properties; further studies are needed to confirm these properties. The result of our study can be used for the development of NSAIDs as potential inhibitors of estrogen receptors. Acknowledgments This research is conducted independently, no funding was received for carrying out this work.