The aim of this study was to evaluate the prognostic role of Forkhead box A1 (FOXA1) in breast cancer and determine the relationship between FOXA1 and zinc finger of the cerebellum 1 (ZIC1). BCIP, GEPIA, and Oncomine databases were used to detect expression of FOXA1 and assess prognostic roles of FOXA1 and ZIC1 in invasive breast tumors. A total of 113 female invasive breast cancer cases were collected to investigate FOXA1 and ZIC1 expression via immunohistochemistry. Twenty pairs of frozen-thawed tumors were used to select reliable indicators via western blotting and real-time quantitative polymerase chain reaction. In addition, Kaplan-Meier curves and Cox regression analysis were performed to analyze the overall survival (OS) and relapse-free survival. Multiple databases showed that FOXA1 expression was elevated in invasive breast cancer and negatively related to ZIC1. BCIP database also displayed a poor prognosis of high FOXA1 and low ZIC1. FOXA1 was positively associated with tumor size, grading, lymph node metastasis, and Tumor Node Metastasis (TNM) staging, while ZIC1 expression was negatively related to grading, lymph node metastasis, and TNM staging. In Kaplan-Meier and Cox regression analysis, FOXA1 negative group and ZIC1 positive group had better OS rate and recurrence-free survival rate. In addition, a joint evaluation showed that "FOXA1- ZIC1+" had the highest OS and relapse-free survival, but "FOXA1+ ZIC1-" had the lowest ones. FOXA1 was negatively related to ZIC1 in breast cancer and they had different roles in clinicopathology and prognosis. Combined examination of FOXA1 and ZIC1 could bring more benefit to breast cancer patients.,Copyright © 2020. Published by Elsevier Inc.