The heterogeneous nuclear ribonucleoprotein C1/C2 is one of the most abundant proteins in the nucleus, and shown to have roles in cellular differentiation and proliferation through post-transcriptional regulations of certain mRNA species. We studied its role in stress response using siRNA mediated knockdown approach in HeLa cells. Upon transient transfection with plasmid encoding siRNA, the cells showed increased sensitivities to various chemical agents, namely H(2)O(2, )paraquat, camptothecin, ICRF-193 and halogenated deoxyuridines. These results demonstrate that hnRNP C1/C2 is involved in maintenance of cellular homeostasis besides cellular differentiation and proliferation.