BACKGROUND RACK1 has been shown to be able to interact with some key cellular proteins involved in tumor development and progression. Our study showed that the expressions of RACK1 and CD147 are correlated with each other. The purpose of this study is to clarify the relationship between expression of RACK1 and CD147 in 180 patients with operable stage T1 human pulmonary adenocarcinoma and their clinicopathological features and prognostic significance. METHODS DNA transfection and RNA interference of RACK1 were conducted to produce pulmonary adenocarcinoma cell lines with differential RACK1 expression. Western blot and RT-PCR were used to quantify RACK1 and CD147 expression in protein and mRNA levels in pulmonary adenocarcinoma cell lines. Immunohistochemistry, double-labeling immunofluorescence, confocal laser scanning microscopy, and Western blot were used to correlate the clinicopathological significance of RACK1 and CD147 expression in cases of stage T1 pulmonary adenocarcinoma. RESULTS We detected high levels of RACK1 and CD147 mRNA as well as protein expression in pulmonary adenocarcinoma in vitro. In pulmonary adenocarcinoma, the expression of RACK1 and CD147 were correlated both in vitro and in vivo. Our clinicopathological analysis demonstrated that RACK1 or CD147 expression correlated with higher incidence of lymph node metastasis and lower differentiation than tumors that were negative for expression of either RACK1 or CD147. The expression of RACK1 and CD147 was not associated with the patient age or gender. Multivariate analysis demonstrated that the co-overexpression of RACK1 and CD147 was an independent prognostic factor for stage T1 pulmonary adenocarcinoma (P = 0.012). CONCLUSIONS Tumor invasiveness is associated with expression of RACK1 and CD147 in pulmonary adenocarcinoma. The co-expression of RACK1 and CD147 could be an important prognostic biomarker for stage T1 pulmonary adenocarcinoma.