Objective: To investigate the As4S4 induced growth inhibition and apoptosis in HeLa cells and its possible relationship with cyclooxygenase-2 (COX-2). Methods: HeLa cells were treated with various concentrations (7.5, 15, 30, 60 mg/L) of As4S4 at different times (12, 24, 36, 48, 60 h). Cell growth was measured by MTT. Apoptosis was detected by double staining flow cytometry (FCM). Levels of PGE2 were measured by radioimmunoassay. The expression of COX-2 protein was examined by West blot analysis. Results: After treated with different concentrations of As4S4, the growth of HeLa cells was suppressed significantly in a dose-and time-dependent manner. The IC50 of 24 h was 30 mg/L (P＜0.01). As4S4 induced apoptosis with apoptosis rates at 8.13%-62.36% by flow cytometry (FCM) in a dose-dependent manners. The release of PGE2 was reduced in HeLa cells with the values being (70.56±2.03), (48.58±2.28), (29.25±1.57) and (18.02±1.04) respectively, significantly different compared with control group (3.15±0.01) (P＜0.01). As4S4 also inhibited the activity and expression of COX-2 in a dose dependent manner and down-regulated the expression of COX-2 protein greatly. Conclusion: As4S4 could inhibit the proliferation and increase apoptosis in human HeLa cells. These effects may depend on the inhibition of the expression of COX-2 and PGE2 by As4S4.