Abstract: Aim ：To investigate the roles of urocanic acid-modified chitosan(UAC)-mediated wild-type p53(wt-p53) gene transfection in inhibiting the proliferation and inducing the apoptosis of human lung adenocarcinoma cell line H1299(p53-null). Methods ：Following UAC-mediated wt-p53 gene transfection in H1299 cells，the expression of green fluorescent protein(GFP)，wt-p53 mRNA and protein was assayed by fluorescence microscopy，RT-PCR and Western blotting，respectively；cell growth inhibition was analyzed by MTT assay；and apoptosis was assessed by DAPI staining and agarose electrophoresis. Results ：UAC-mediated wt-p53 gene transfection in H1299 cells resulted in the appearance of many cells expressing GFP，the notable increases of wt-p53 mRNA and protein expression levels，the significant cellular growth inhibition，the obvious increased proportion of apoptotic cells and the clear DNA ladder. Conclusion ：UAC-mediated wt-p53 gene transfection could significantly inhibit the proliferation and induce the apoptosis in human lung adenocarcinoma cell line H1299.