OBJECTIVE: To explore the regulatory function and mechanism of CXCL14 in endometriosis. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the expression of CXCL14 in eutopic and ectopic endometrial stromal cells (ESCs) derived from patients with endometriosis and in situ endometrial stromal cells derived from healthy individuals. Alterations in cell proliferation and migration capabilities were assessed through Cell Counting Kit-8 (CCK8) and transwell assays following the silencing or overexpression of CXCL14. Mass spectrometry was employed to identify potential interacting proteins of CXCL14, and proliferating cell nuclear antigen (PCNA) was selected for further investigation. The regulatory mechanism of PCNA by CXCL14 was further examined using co-immunoprecipitation (co-IP), Western blotting, and cellular experiments. RESULTS: CXCL14 was highly expressed in ovarian endometriosis. The proliferative and migratory abilities of ESCs were positively correlated with CXCL14 expression levels. Moreover, CXCL14 interacted with PCNA. Silencing CXCL14 expression increased PCNA ubiquitination and promoted its degradation. Conversely, overexpression of PCNA mitigated the inhibitory effects of CXCL14 silencing on ESCs. CONCLUSIONS: CXCL14 may regulate PCNA through the ubiquitination pathway, thereby promoting the development and progression of endometrial stromal cells. This study provides new insights into the pathogenesis of endometriosis, highlighting the potential of CXCL14 as a therapeutic target.