AIM: To study the influence of frontalis muscle flap suspension on ocular surface by analyzing the clinical features and inflammatory cytokines. METHODS: A prospective, observational case series. Thirty-one eyes of 25 patients with severe congenital blepharoptosis who underwent frontalis muscle flap suspension surgery with at least 6mo of follow-up were included in the study. The main outcome measures were margin reflex distance 1 (MRD1), degree of lagophthalmos, ocular surface disease index (OSDI), fluorescein staining (Fl), tear break-up time (BUT), Schirmer I test, and inflammatory cytokine assay. RESULTS: The degrees of lagophthalmos significantly increased after surgery. The OSDI scores significantly increased 1wk postoperatively and then decreased 4wk after operation. The Fl scores reflected corneal epithelial defects in sixteen patients at early stage postoperatively. The BUT and Schirmer I test values remained stable and did not show change compared to those before surgery. The inflammatory cytokines in conjunctival epithelial cells (including IL-1β, IL-6, IL-8, TNF-α, and IL-17A) significantly increased 1wk after the surgery (P<0.001), then returned to the normal level at 24wk postoperatively. The levels of inflammatory cytokine IL-1β, IL-6, IL-8, TNF-α, and IL-17A elevated significantly and were positively correlated with OSDI and Fl scores. CONCLUSION: Frontalis muscle flap suspension surgery results in lagophthalmos in early period of post-operation and relieved after months. The elevation of inflammatory cytokines level may participate in the occurrence of corneal epithelial defects at the early postoperative stage.