Gonadotropin-releasing hormone receptor (GnRHR) has been identified as a factor that hinders the malignant advancement of triple-negative breast cancer (TNBC). Nevertheless, the specific molecular mechanism responsible for this impact remains unclear. This study demonstrates that GnRHR exhibits low expression levels in TNBC, which correlates with an unfavorable prognosis for patients. GnRHR promotes the expression of FOS, subsequently enhancing IFI44L transcription and expression, thereby inhibiting TNBC cell proliferation, migration, and invasion. Goserelin reduced the growth rate of TNBC tumors in nude mice, resulting in elevated levels of GnRHR, FOS, and IFI44L in tumor tissues, while the expression of Ki67, vimentin, and N-cadherin decreased. Overall, our results reveal that GnRHR suppresses the malignant progression of TNBC by upregulating FOS and IFI44L. Goserelin slows down the proliferation of TNBC tumors in vivo through the GnRHR/FOS/IFI44L pathway, which may present a new therapeutic approach for the management of TNBC.