Abstract: Objective To analyze the clinical features of vulvar squamous cell carcinoma (VSCC) and vulvar subepithelial intraepithelial lesion (VSIL).Methods Clinicopathologic data were collected from patients who were pathologically diagnosed with VSCC, vulvar high-grade squamous intraepithelial lesion (VHSIL), and vulvar low-grade squamous intraepithelial lesion (VLSIL) in Xuzhou Central Hospital from September 2015 to June 2021. Then, the clinical symptoms, lesion sites, colposcopic manifestations, the positivity rate and subtypes of human papillomavirus (HPV) infection in VSCC and VSIL were retrospectively compared, in order to analyze the clinicopathological features of patients with VSCC.Results The average age of patients with VLSIL, VHSIL and VSCC were 45.81±18.12, 54.76±18.74 and 65.59±14.61 years, respectively, with statistical differences (P<0.05). Patients in the VSCC, VHSIL and VLSIL groups mostly presented vulvar itching and pain, where 69.57% of VSIL lesions were located in the posterior vulvar union area and 68.18% of VSCC lesions were located in the labia majora. Colposcopic vinyl white reaction: 100% in the VLSIL group, 88.00% in the VHSIL group and 90.91% in the VSCC group. Vascular signs: 4.76% of VLSIL and 20.00% of VHSIL had punctate vasculature-like structures, whereas 77.27% of VSCC had punctate or heterogeneous vascular images. HPV infection rate: 100% in the VLSIL group, 76.00% in the VHSIL group, and 40.90% in the VSCC group, and the VHSIL and VSCC groups presented higher HPV16 positive rates than the VLSIL group (P<0.05). Compared with the HPV-positive VSCC group, the HPV-negative VSCC group was older, and showed an increased percentage of poorly differentiated tumors, and an increased percentage of FIGO stage Ⅲ—Ⅳ, with statistical differences (P<0.05).Conclusions VSCC and VSIL patients commouly show vulvar itching, plaques, and HPV16 infection, with predominantly vinegar-white signs in colposcopy, and vascularized structures were obvious in VSCC. Vulvar area and colposcopy are needed to improve early diagnostic rate. HPV-negative VSCC has a lower tumor grade and later tumor stage, and HPV-based risk stratification of VSCC should be emphasized.