Objective: To investigate the relationship of loss of P16 expression with biologlical behaviors and prognosis of gastrointestinal stromal tumors(GISTs). Methods: The expression of P16 protein and mRNA was detected in GISTs tissues by immunohistochemistry,Western blot and RT-PCR.The prognosis was evaluated through follow up. Results: The expression rates of P16 protein and mRNA in GISTs were 53.8%(21/39，Frozen tissue)，51.3%(20/39，Frozen tissues)and 51.4%(37/72，Paraffin-embedded tissues)，respectively.The expression of P16 was significantly different among GISTs of different aggressive risk(P<0.05).With the incease of aggressive risk，the expression of P16 was deceased.The expression of P16 was negtively correlated with Ki-67 and patient survival(P<0.05). Conclusion: The loss of P16 expression has a positive correlation with the infiltration and progression of GIST.Detection of P16 protein and mRNA is helpful for the evalutaion of biological behaviors and prognosis of gastrointestinal stromal tumors.