Aim: To investigate the effect of benzothiazole derivatives (Rosline) on ovarian cancer and the potential mechanism. Methods: Ovarian cancer tissues were collected clinically and immunohistochemistry was used to detect the expression of p53 and p21. Ovarian cancer cells were exposed to 0, 2.5, 5, 10 mu mol/L Rosline for 24 h. 100 nmol/ L Pifithrin-alpha pre-incubation was used to inhibit the transcriptional activity of p53. CCK-8 and BrdU assays were used to detect the effects of different concentrations of rosline on the proliferation and cell cycle of OVCAR420 and SKOV3 cells. Flow cytometry assay was used to detect cell cycle. The transcriptional and translational expression of p21 and p53 were detected by RT-qPCR and Western blot. Results: p21 was expressed in ovarian cancer tissues without p53 expression. Rosline inhibits the proliferation of ovarian cancer cells and blocks the cell cycle progression. Meanwhile, Rosline promotes p21 expression in ovarian cancer cells at both mRNA and protein levels, but with no significant effect on p53 expression. Besides, Rosline promotes p21 expression, inhibits cell proliferation, and blocks the cell cycle via the p53-independent pathway. Conclusion: Rosline promoted p21 expression thereby inhibiting cell proliferation and blocks the cell cycle via p53-independent pathway.