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Background: The prognostic significance of CD44 variant-9 (CD44v9) expression in human cancers has been investigated in several studies, however, definite conclusion has not be reached. The aim of this systematic review and meta-analysis was to evaluate the prognostic significance of CD44v9 expression in various cancers., Methods: Three common databases were searched and retrieved studies were assessed using the inclusion and exclusion criteria. The further analyses for overall survival (OS), recurrence-free survival (RFS), and clinicopathological parameters were performed., Results: Fifteen studies containing 1633 cancer patients were included into this research. Patients with positive CD44v9 expression tended to have shorter OS (hazard ratio [HR] = 1.93, 95% confidence interval [CI] = 1.48-2.52, P < .01) and RFS (HR = 3.60, 95% CI = 1.52-8.53, P < .01) when compared with patients with negative CD44v9 expression. Positive CD44v9 expression was associated with larger tumor size (P = .04), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), and more advanced clinical stage (P < .01) when compared with negative CD44v9 expression., Conclusion: Positive CD44v9 expression predicted worse prognosis in human cancers compared with negative CD44v9 expression. CD44v9 expression could serve as a prognostic factor of human cancers.