Objective To investigate the anti-tumor effect of doxycycline against ovarian cancer cells and the underlying mechanism. Methods MTT assay was used to test the tumor cell viability after treated with doxycycline alone or in combination with cisplatin. RT-RCR was used to examine CXCR4 mRNA expression in HO8910 cells. Western blotting analysis was used to determine CXCR4 protein expression after doxycycline treatment. Results Treatment with low dose of doxycycline (10 μg/mL) for 48 hours notably inhibited the proliferation of ovarian cancer cell HO8910 (P<0.01), with the inhibition rate being (70±2)% when doxycycline concentration was at 50 μg/mL. Doxycycline combined with cisplatin had greater inhibitory effect against HO8910 cells compared with cisplatin alone at the same concentration. Doxycycline treatment down-regulated CXCR4 expression in HO8910 cells. Conclusion Doxycycline has a definite inhibitory effect against proliferation of ovarian cancer HO8910 cells, and it can increase the sensitivity of tumor cells to cisplatin, which may involve SDF-1/CXCR4 signaling pathway.