Molluscum contagiosum (MC) is an infectious disease caused by the MC virus. In human immunodeficiency virus (HIV) patients, MC has an atypical predilection and prominence, sometimes measuring more than 1 cm in diameter, known as giant MC. Giant MC lesions on the eyelids are rare. There is no standardized therapy for eyelids MC in HIV patients. Antiretroviral (ARV) administration is recommended as the primary treatment for MC in HIV patients along with other treatment modalities, such as potassium hydroxide (KOH). The 20% KOH solution is a keratolytic agent with good efficacy as MC therapy. Two cases of giant MC on the eyelids of stage 2 HIV patients with respective CD4+ of 31 cells/μL and 46 cells/μL were reported. The lesions consisted of multiple confluent papules with central umbilication, and Tzanck smear revealed Henderson-Patterson bodies. Both patients were treated with ARV and self-applied 20% KOH solution once daily. The lesions improved after four weeks of therapy in both patients with most of the lesions diminished. The successful treatment with 20% KOH solution for giant MC on the eyelids of HIV patients observed in the current study provides evidence that treatment with this solution yielded prompt results, is non-toxic, and can be self-applied.