This review aims to summarize the current knowledge with regard to the expression and prognostic implications of the ERs in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the EGFR, and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Here, EGFR is linked to lung cancer.