The pleural effusion is an occasion clinical presentation of tuberculosis and lung cancer and clear differentiation of this condition is critical, as it appeared as typical lymphocytic pleural effusion in both diseases. There is a dominance of Th1 response in tuberculous pleurisy, a matter which encourages the evaluation of Th1 cytokines in order to reveal a possible diagnostic tool. Interferon-gamma (IFN-γ) as a major product of Th1, Interleukin- 12 (IL-12) and (IL-18) as IFN-γ inducing cytokines were evaluated in 39 patient's pleural effusions (10 tuberculous and 29 lung cancer) using ELISA. Our results demonstrated significantly increased levels of IFN-γ, IL-12 and IL-18 in tuberculous pleural effusions compared with those of malignancies. Moreover, it was found that IFN-γ is strongly correlated (r=0.71) with IL-12. The Receiver-Operator-Characteristics (ROC) analysis explored great areas under curves (AUCs) for the three cytokines suggesting diagnostic marking for tuberculous pleurisy differentiating it from malignant one. The most reliable cytokine in the diagnosis was the IFN-γ as it appeared at ROC of 0.93 followed by IL-12 and IL-18 which contribute to 0.80 and 0.71 ROC's, respectively. A larger study including more cytokines regarding Th1 and Th2 products is recommended.