Silver nanoparticles (AgNPs) are nowadays incorporated in a large number of consumer and medical products. Several experiments demonstrated that AgNPs cause toxicity to various cells via induction of reactive oxygen species (ROS). The present study was aimed to evaluate the mechanistic view of AgNPs’ toxicity in A549 cells including the ROS-dependent and -independent pathways using a ROS scavenger, N-acetyl cysteine (NAC). Cytotoxicity test (MTT assay) showed that AgNPs significantly (P < 0.05) reduced cell viability in a concentration and time-dependent manner. AgNPs (100 and 200 µg/ml) significantly (P < 0.05) increased ROS formation which could be attenuated by NAC. Mitochondrial membrane potential (MMP), as measured by tetramethyl rhodamine ethyl ester (TMRE) assay at 24, 48 and 72 h was significantly (P < 0.05) reduced in AgNPs (100 and 200 µg/ml) treated groups in the concentration and time-dependent manner. NAC prevented the declination of MMP of AgNPs (100 µg/ml) treated group. Cell cycle analysis at 24, 48 and 72 h revealed the significant (P < 0.05) increment of subG1 and S phase population in treated cells and this subG1 ratio could be attenuated by NAC (P < 0.05). Interestingly, no statistical significant difference of S-phase population was observed between NAC-pretreated groups and that of the control. To provide mechanistic view of AgNPs-induced S phase arrest, the expression level of cell cycle-associated protein, proliferating nuclear antigen (PCNA) was investigated. PCNA expression was significantly (P < 0.05) concentration-dependent down-regulated by AgNPs and NAC could not prevent this effect. These observations allow us to envisage a possible scenario of AgNPs-induced cytotoxicity in A549 cells via both ROS-dependent and ROS-independent pathways. Experiments to elucidate mechanism of AgNPs-induced toxicity should be further performed.