Precancer biomarkers help in early detection and management of oral potentially malignant disorders (OPMDs). Interleukin-1β (IL-1β), a biomarker, is known to be altered in oral submucous fibrosis (OSMF) and oral leukoplakia (OL). Therefore, we evaluated and compared the serum and salivary IL-1β levels in patients with OSMF/oral leukoplakia and in gender- and age-matched healthy individuals. An in vivo, prospective, observational study was conducted on 40 subjects. Subjects were divided into two groups with 20 individuals in each group, that is, Group I: OSMF/oral leukoplakia and Group II: control group. Salivary and serum IL-1β levels were quantitatively estimated using enzyme-linked immunosorbent assay (ELISA). The statistical tests used were unpaired t-test and Chi-square test. The serum IL-1β levels were significantly (P 0.001) lesser in Group I in comparison to Group II. The salivary IL-1β levels remained insignificant between both the groups. However, in both the groups, the salivary IL-1β levels were significantly higher compared to the serum IL-1β levels. We found that the serum IL-1β level can be considered as a prospective biomarker for dysplasia, whereas salivary IL-1β alone needs more elaborated studies to account for its application as a potential biomarker in OPMD.