A ranula is a pseudocyst that originates from the sublingual gland after trauma. Acute cases of ranulas that progress rapidly and cause respiratory distress are rare. Holoprosencephaly is a complex brain malformation caused by incomplete cleavage of the prosencephalon. Children with holoprosencephaly may experience upper airway obstruction due to the associated dentoalveolar malformations and oromotor dysfunctions. We present the case of an eight-year-old female patient with holoprosencephaly and a plunging ranula that manifested as an acute course due to difficult airway management. She required gastrostomy for oromotor dysfunctions related to feeding and swallowing and difficulty managing oral secretions. The sublingual gland and ranula were removed under general anesthesia. Postoperatively, urgent reintubation and close monitoring in the intensive care unit were required due to upper airway obstruction. We successfully managed the patient with close cooperation of a pediatrician and an anesthetist, and no recurrence was observed at the one-year follow-up. A ranula can be caused by trauma to the floor of the mouth in association with lingually inclined mandibular teeth, a type of dentoalveolar compensation seen in maxillary hypoplasia associated with holoprosencephaly. Careful consideration is needed in such cases since airway management can be difficult due to postoperative swelling and oromotor dysfunctions.