Background Leukokeratosis of the vocal cords is a clinical descriptive diagnosis, which includes a group of squamous intraepithelial lesions of the vocal cord mucosa. We investigated the clinical classification and treatment efficacy of leukokeratosis of the vocal cords. Methods We conducted a retrospective analysis of the medical history, laryngoscopic examinations, morphological features under a surgical microscope, and pathology results of 360 cases of leukokeratosis of the vocal cords to examine correlations among treatment modalities, therapeutic effects, and clinical features. Results All cases were divided into four types based on symptoms, examination results, and treatment efficacies as follows: 21 patients had type I inflammatory leukoplakia and their vocal cord morphology and voice quality recovered after conservative therapies; 76 patients had type II frictional polyps and received CO2 laser subnnucosal cordectomy; 68 patients had type III sulcus vocalis and received mucosal slicing with dredging; and 195 cases had type IV simple leukokeratosis and received partial subligamental cordectomy with CO2 lasers or transmuscular cordectomy. Our treatment achieved a surgical cure rate of 90.9% (308/339), with a recurrence rate of 9.1% (31/339) and malignant transformation rate of 6.5% (22/339). All cancerous transformations occurred in type IV patients. Conclusion Choosing conservative or CO2 laser surgery based on the morphological characteristics of squamous epithelial lesions of keratinized vocal cord mucosa can maximally protect voice quality, reduce complications, and improve the cure rate.