We previously reported that flotillin-1 facilitates lymph node metastasis in cervical cancer, but the role flotillin-1 plays in carcinogenesis and metastasis in vulvar squamous cell carcinoma remains unclear. In the current study, we performed immunohistochemistry (IHC) staining in 70 paraffin-embed vulvar squamous cell carcinoma tissues. Expression of flotillin-1 protein is significantly up-regulated in vulvar squamous cell carcinoma tissues. Expression profile of flotillin-1 protein associates with FIGO stage, inguinal and/or femoral lymph node metastasis, extracapsular nodal spread and numbers of metastatic lymph node. High expression of flotillin-1 protein predicts poor PFS and OS in patients with vulvar squamous cell carcinoma and serves as an independent prognostic factor predicting poor PFS. These data implicate that flotillin-1 may play an oncogenic role in vulvar squamous cell carcinoma by facilitating inguinal and/or femoral lymph node metastasis; high expression of flotillin-1 protein may serve not only as a potential predictor of lymph node metastasis, but also as a promising prognostic risk factor for patients with vulvar squamous cell carcinoma.