Lung cancer is the leading cause of cancer-related deaths and its treatment is based in chemotherapy using platinum containing compounds, mainly cisplatin (CDDP). Many patients show resistance to CDDP leading to treatment failure. To understand the mechanisms involved in CDDP resistance in lung cancer, we used CDDP-sensitive (A549) and –resistant (A549/CDDP) cells to identify newly synthesized proteins in response to CDDP treatment using BONCAT technique. In addition the steady-state proteome of A549 and A549/CDDP cells was also evaluated. It was identified 70 and 69 proteins upregulated by CDDP in A549 and A549/CDDP cells, respectively. The set of proteins upregulated by CDDP in both cells are associated to GO terms related to proteostasis, telomere maintenance cell, RNA processing, cytoskeleton and response to oxidative stress. Interestingly, the profile of biological processes enriched in A549 cells after CDDP treatment is very similar to those identified in the steady-state proteome of A549/CDDP cells, suggesting their positive selection in CDDP-resistant cells development. Therefore, this study of proteomic response to CDDP is relevant to the identification of potential protein targets to development of therapeutic strategies to block drug resistance pathways.