Objective To explore therapeutic effect of focused ultrasound combined with Hypocrellins in patients with non-neoplastic intraepithelial lesions of vulva. Methods Totally 80 cases of non-epithelial tumor like lesions of epithelium were admitted in our hospital from December 2010 to December 2015. All patients received focused ultrasound treatment as standard treatment. Patients in observation group received additional treatment of Hypocrellins. Levels of P16 and CD34 in tissues were measured. Results Treatments induced decreased levels of scores of vulvar pruritus, skin elasticity score and area of white lesions of vulva in the two groups; additional treatment of Hypocrellins in observation group induced more significant improvement when compared with control group (P < 0.05). All patients experienced increased levels of P16 protein and decreased levels of CD34 protein compared with those prior to any treatments. Still, treatment with Hypocrellins induced dramatical increase of P16 and decrease of CD34 compared with control group. Conclusions Focused ultrasound combined with Hypocrellins exerts promising therapeutic effect in treatment of NNED through manipulating cell cycle and microcirculation.