A diet derived agent Curcumin (Diferuloylmethane), demonstrated its clinical application in inflammation, infection and cancer conditions. Nevertheless, its impact on the proteome of epithelial cells of non-small cell lung carcinoma (NSCLC) still needs further attention. We employed a stable isotope labeling method for cell culture (SILAC) based relative quantitative proteomics and informatics analysis to comprehend global proteome change in A549 cells treated to curcumin and/or Lipopolysaccharide (LPS). Pretreated A549 cells were infected with Mycobacterium tuberculosis H37Rv strain to monitor bacterial entry and load. With exposure to curcumin and LPS, out of the 1492 identified proteins, 305 and 346 proteins showed deregulation respectively. The expression of BID and AIFM1 mitochondrial proteins which play critical role in apoptotic pathway was deregulated in curcumin treated cells. A549 cells treated with curcumin showed higher active mitochondria intensity with respect to LPS treatment. Simultaneous treatment of curcumin and LPS neutralized the effect of LPS. Infection of pretreated A549 cells with Mycobacterial H37Rv strain, showed successful internalization with varied bacterial load. Treatment with both curcumin and LPS had similar bacterial load as control cells. This study generated evidence to deepen our understanding on anti-inflammatory role of curcumin and identified targets might be useful as drug targets.