Lung cancer is one of the leading causes of cancer death in the world. Human non-small-cell lung carcinoma (NSCLC) accounts for almost 80% of lung cancer cases. Aberrant phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathways play important roles and have been widely observed in the development of NSCLC. Previous studies indicated that garlic extracts such as diallyl disulfide (DADS) and diallyl trisulfide (DATS) could inhibit the proliferation of several types of cancer in vitro. However, the inhibitory effects of S-allylcysteine (SAC) on the growth of NSCLC have not been demonstrated yet. Therefore, this study investigated whether consumption of SAC could prevent the growth of NSCLC in both in vitro and in vivo models. It was found that SAC significantly inhibited the proliferation of human NSCLC A-549 cells in vitro. Treatment of the NF-κB inhibitor, Bay-11-7082, could significantly inhibit the proliferation of NSCLC A-549 cells. The results demonstrated that SAC significantly suppressed the activation of mTOR, NF-κB, and cyclin D1 molecules in vitro. Furthermore, the results demonstrated that consumption of SAC significantly inhibited the growth of highly metastatic human NSCLC cells in tumor-bearing mice. Bioluminescence imaging and pathological and immunohistochemical (IHC) staining results also indicated that SAC could effectively suppress the growth and malignant progression of human NSCLC in vivo. The chemopreventive effects of SAC were associated with suppression of mTOR and NF-κB molecules in vivo. These results suggested that SAC could act as an effective agent against the malignant progression of human NSCLC in both in vitro and in vivo models.