Fine particles (PM2.5) have generally been reported as the major contributor to the adverse health effects of air pollution. Lebanon is characterized by a high density of transport, the production of electricity by generators, and a problem of uncontrolled incineration of household waste. For the purpose of this paper, the physico-chemical properties of fine (PM2.5-0.3) and quasi-ultrafine (PM0.3) particulate matter sampled in Southern Lebanon, were studied. Then, an evaluation and comparison of the toxicity of the different extracted fractions from PM (i.e., native PM2.5-0.3 vs. organic extractable matter fraction (OEM2.5-0.3), and non-extractable matter fraction (NEM2.5-0.3)) was performed. Also, an examination of the toxicity of PM0.3 was conducted indirectly through the evaluation of the OEM0.3 harmfulness. The physico-chemical analysis showed that PM0.3 was much more concentrated than PM2.5-0.3 in organic compounds such as polycyclic aromatic hydrocarbons (PAHs) (28-fold) and their nitrated (N-PAHs, 14-fold) and oxygenated (O-PAHs, 10-fold) derivatives. Normal human bronchial epithelial cells (BEAS-2B) were exposed to PM2.5-0.3, its derived fractions (i.e., OEM2.5-0.3 and NEM2.5-0.3), and OEM0.3 before evaluating the global cytotoxicity, metabolic activation of organic compounds, genotoxicity, and inflammatory response. Different responses were observed depending on the considered fraction of particles. The global cytotoxicity showed a pronounced response related to ATP and LDH activities after exposure to the quasi-ultrafine organic extractable matter fraction (OEM0.3). There was no significant induction of the AhR cell-signaling pathway by NEM2.5-0.3. Despite the apparent difference in the kinetics of induction of the toxicological endpoints under study, OEM0.3 provoked a higher overall cytotoxicity and genotoxicity than OEM2.5-0.3 and total PM2.5-0.3. Taken together, these results clearly showed that the finest particles are more damaging to BEAS-2B cells than PM2.5-0.3 because they are richer in organic compounds, thereby inducing more remarkable toxic effects.