In order to determine the relationship between P16 and the tumorigenesis of malignant lymphoma，silver-stained PCR-SSCP analysis and direct sequencing were used to evaluate the alterations of P16 gene in 8 human malignant lymphoma cell lines. A homolygous loss was found in SU-DHL-9 while mutations of P16 exon 2 in SU-DHL-1 and Daudi. Sequencing of the PCR-product showed three point mutations in SU-DHL-1，which were GAC to AAC in codon 72，GOT to ACT in codon 77，and a insertion of C between codon 82 and 83，respectively. This study suggested the mutations of P16 gene are highly frequent in B-cell lymphoma cell lines and may play an important role in its tumorigenesis.