Aim: Develop and validate a method of solid-phase microextraction (SPME) and liquid chromatography to investigate three major polycyclic aromatic hydrocarbons (PAHs) in oral fluid. Results/Methodology: The extraction phase was exposed to 1.5 ml of diluted oral fluid under stirring at 1000 rpm for 60 min, at 70°C. Then, it was immersed in 200 μl of acetonitrile for 10 min at 25°C for desorption of the analytes. Linearity, absolute recovery, and inter- and intra-assay relative standard deviations and relative errors were 50–300 ng.ml^-1, ≥24% and ≤15% for all analytes, respectively. A full factorial design was used to SPME optimization. Discussion/Conclusion: The method is suitable for the exploratory analysis of some PAHs in the oral fluid of crack smokers.