About 60 components in cigarette smoke are considered to be carcinogens, namely polycyclic aromatic hydrocarbons, nitrosamines, aromatic amine, trace metals, as well as nicotine. Nicotine is considered to be one of the active components in cigarette smoke, and its association with tumorigenesis is enigmatic. Nonsteroidal antiinflammatory drugs are widely accepted as antitumor agents to treat patients with cancer by inhibiting cyclooxygenase-2 activity. Stimulation of tumor growth by nicotine involves different processes of cell proliferation and angiogenesis. Study results, with the use of animal xenograft models and cell culture systems, show that nicotine stimulates the progression of tumor growth, through a cyclooxygenase-2–dependent pathway. On the basis of these findings, nicotine seems to be a potent mitogenic agent in modulating tumor cell proliferation, and selective cyclooxygenase-2 inhibitors are promising antitumor agents for gastric cancer in smokers.