To address the functions of SigN (SCO4034) in Streptomyces coelicolor, we constructed a sigN null mutant M145Z, which showed a defect in sporulation. The differential proteomic profiles of wild-type S. coelicolors M145 and M145Z were demonstrated by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), which identified 24 different spots that were up- or down-regulated due to sigN disruption. Among them, 22 proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The up-regulated proteins were involved in energy metabolism, stress responses, ATP binding, ppGpp stringent stress response and transcriptional anti-termination, etc. The down-regulated proteins were related to antibiotic synthesis and differentiation. The results gave a new insight into the regulatory mechanism of SigN in S. coelicolor. Furthermore, deletion of sigN caused growth retardation under all stress conditions examined including heat, cold, acid, oxidation, salt and ethanol. These results indicated that SigN was involved in morphological development, secondary metabolism and stress responses in S. coelicolor.