Abstract Objective It is estimated that the mortality rate from tobacco-related diseases will reach 10 million worldwide by 2030. It is validated that every three out of four oral cancers are caused by the use of tobacco in various forms especially smoking. Early detection is the only way to reduce this burden. Molecular-level analysis has currently become a valuable tool in the diagnosis and prognosis of diseases. Around 1000 different salivary protein biomarkers are being investigated in saliva for this purpose. Some of these markers are being investigated to evaluate the proportionality of cigarette smoking. The objective of this study was to evaluate the levels of salivary biomarker interleukin-8 (IL-8) among smokers and nonsmokers as a control group. Materials and Methods This is a comparative cross-sectional study conducted in Islamabad Dental Hospital, Bhara Kahu. A total of 60 patients were recruited and divided into two equal groups of smokers and nonsmokers. Unstimulated saliva samples were collected and analyzed using an enzyme-linked immunosorbent assay kit. Statistical Analysis The results were then analyzed by SPSS v25 using an independent sample t-test to evaluate the statistical difference and significance. Results A p-value (<0.001) was found to be significant for the IL-8 levels in smokers when compared with nonsmokers. The mean value for smokers was found to be 122.69 pg/mL and the mean for nonsmokers was evaluated to be 20.68 pg/mL. Conclusion As the levels of IL-8 were high, it was concluded to be an effective biomarker for the evaluation of smoking-based initial inflammatory changes detectable from saliva.