In domestic ruminants, a receptive endometrium is crucial for successful pregnancy. Although many essential molecular modulators and pathways have been identified during early pregnancy, the precise mechanisms regulating goat endometrial function remains largely unknown. Here, we describe a novel regulator during early pregnancy, whereby hormones increased CREB3 regulatory factor (CREBRF) expression and act as a potential activator of autophagy in endometrial epithelial cells (EECs) via the mTOR pathway. Our results showed that knockdown of CREBRF via shCREBRF hampered EECs proliferation by S-phase cell cycle arrest and significantly inhibited endometrial function. We also reported that CREBRF-mTOR-autophagy pathway plays a vital role in regulating endometrial function, with a blockade of the mTOR by rapamycin demonstrating the regulatory function on prostaglandin (PGs) secretion and cell attachment in EECs. Moreover, chloroquine pretreatment also proved the above conclusion. Collectively, our findings provide new insight into the molecular mechanisms of goat endometrial function and indicate that the CREBRF-mTOR-autophagy pathway plays a central role in PGs secretion and cell attachment.