Previous studies have suggested a link between the presence of Candida invasion and oral premalignant lesion. The objective of the current study was to investigate the clinicopathologic features of candidal infection in biopsies of a large retrospective cohort of patients with premalignant oral leukoplakia (n = 396) from eastern China and assess the clinical implications. Candidal hyphae were detected with periodic acid-Schiff staining of the biopsy samples. The results showed that 59 patients (15.9%) with oral leukoplakia were infected by Candida. The average age of the patients with candidal leukoplakia was 60.7 years with equal sex ratio. The tongue was the predominant site (66.1%). Epithelial hyperplasia and dysplasia were involved in 44.1% and 55.9% of patients, respectively. Multivariate analysis revealed that patient older than 60 years (odd ratio [OR], 2.28; P = .005), lesion located at the tongue (OR, 1.89; P = .038), and presence of dysplasia (OR, 2.02; P = .018) were significant risk factors of candidal infection in oral leukoplakia. Collectively, clinicopathologic features of candidal leukoplakia in eastern China were elucidated. A point to highlight was that we identified a subpopulation that was more liable to candidal infection. Elderly patients with oral tongue leukoplakia with epithelial dysplasia had much higher risk of candidal infection. Antifungal therapy was further recommended to be routine treatment of this subpopulation.