Abstract: Objective:To investigate the expression and significance of midkine (MK) protein in human gastric cancer, and to discuss the relationship and molecular mechanism between MK expression and proliferation of SGC7901 gastric cancer cells. Methods:Real-time quantitative RT-PCR was used to detect the level of MK mRNA expression in clinical spec-imens and matched normal mucous tissues of 140 cases with human gastric cancer. Molecular cloning technology was used to construct a recombinant retrovirus vector containing the human midkine gene. The clone was sequence verified, then transfected to the GP293 viral encasing cells using Lipofectamine2000 and the viral supernatant was collected 48 hours later. Viral supernatant of different concentrations was used to infect the SGC 7901 cells separately. MTT assay was used to investigate the effect of MK on the proliferation of SGC 7901 cells. Western blot assay was used to determine the expression of MK after infection with different concentrations of retrovirus and to detect the molecular mechanism of the MK affecting the growth of gastric cancer cells. Results: In 46of the 70gastric cancer patients ( 65.7%), the up-regulation of MK expression was 2 times higher in the tumor than in the matched normal mucous tissue. In only 8 of the 70patients (11.4%), the up-regulation of the MK expression was 2 times higher in the matched normal mucous tissue than in the tu -mor, with statistically significant differences between the two (P<0.05). With an increase in the concentration of retrovirus, the MK expression level gradually rose. At the same time, the proliferation of SGC 7901 cells grew faster and faster. With an increase in the MK expression, the expressions of the ubiquitin ligase CBL and CBL-b were down-regulated, while the phosphorylated Akt was clearly up-regulated. Conclusion : MK is highly expressed in gastric cancer. Retroviral infection of the SGC 7901cells may significantly increase the proliferation of gastric cancer cells. By the way of dose dependence, MK down-regulates the expressions of CBL and CBL-b, and concurrently up-regulates the Akt activity, inferring that MK can relieve its ubiquitin degradation of the PI3 kinase, and thus activate the PI3K/Akt signaling pathway and decrease the growth of tumor cells.