FOXQ1 (forkhead box Q1) is a forkhead transcription factor, and FOX genes play significant roles in a series of biological processes. The aim of our study was to verify the importance of FOXQ1 as a prognostic indicator in HCC patients. One-step quantitative real-time PCR was performed to identify the expression of FOXQ1 mRNA in HCC and corresponding non-cancerous tissues. FOXQ1 expression was then evaluated by immunohistochemistry (IHC) using tissue microarray. Finally, we analyzed FOXQ1 expression and clinicopathological factors in 114 HCC patients using SPSS 20.0 software. FOXQ1 expression at the transcriptional level in HCC cells was much higher than in the noncancerous cells (P=0.012, respectively). Comparison of clinicopathological characteristics and FOXQ1 expression in HCC by IHC and χ(2) tests showed that high FOXQ1 expression was linked to large tumor diameter, high serum α-fetoprotein levels and later stage grouping with tumor node metastasis classification. Kaplan-Meier and Cox regression analyses showed that high FOXQ1 expression and regional lymph node metastasis were independent prognostic factors. Our study demonstrates that an aggressive malignant phenotype of HCC is strongly linked to high FOXQ1 expression, and FOXQ1 may be a novel target in HCC therapy. Furthermore, it is likely that FOXQ1 is an oncogene in HCC.