Purpose: To report a case of fibrinous acute anterior uveitis associated with topical interferon-a2b (IFN-a2b) treatment for ocular surface squamous neoplasia in a patient with HLA-B27 uveitis predisposition.Methods: Case report. Results:We present the case of a 57-year-old man who received topical IFN-a2b as adjuvant therapy for a previously surgically removed ocular surface squamous neoplasia with affected surgical margins. Two weeks after topical IFN-a2b initiation, the patient was diagnosed with fibrinous acute anterior uveitis. Complementary tests to rule out other causes of uveitis resulted to be negative, except for HLA-B27, which tested positive. Response to treatment with topical corticosteroids and cyclopentolate was favorable. As IFN-a2b is considered an immune enhancer and has been widely associated with autoimmune side effects, topical therapy with IFN-a2b was temporally ceased until intraocular inflammation resolved. Topical IFN-a2b was resumed, and during follow-up, no signs of uveitis were detected. The main hypothesis is that IFN-a2b acts as a trigger for intraocular inflammation in individuals with uveitis predisposition.Conclusions: Topical IFN-a2b could trigger intraocular inflammation in patients with uveitis susceptibility. It may be reasonable to use IFN-a2b cautiously in patients with a known history of uveitis or uveitis predisposition.