Abstract: To investigate the effects of total Panax notoginseng saponins ( tPNS ) on the proliferation and migration of PC-3 cells, and to provide experimental evidence for the use of tPNS in treating prostatic cancer. Methods: MTT, cell counting, and wound-healing assays were performed to analyze the effects of tPNS on the proliferation and migration of PC-3 cells. The expression of proliferating cell nuclear antigen ( PCNA ), vascular cell adhesion molecule 1 ( VCAM-1 ), and matrix metalloproteinases 2 ( MMP-2 ) was determined using Western blot analysis or zymography. Activation of p38 MAPK and ERK was also detected by Western blot analysis after tPNS treatment. Results: tPNS inhibited the proliferation of PC-3 cells. The inhibition ratios were 13.0%, 29.5%, and 35.9% after the PC-3 cells were treated with tPNS ( 200, 400, and 800 mg/L, respectively ) ( P < 0.05 ). PCNA expression was also inhibited in dose- and time-dependent manners. These results indicated that tPNS could significantly inhibit PC-3 cell proliferation via downregulation of PCNA. The migration of PC-3 cells was inhibited after treatment with tPNS. The Western blot and zymography results suggested that tPNS significantly suppressed the expression of the migration-related protein MMP-2. VCAM-1 was also downregulated after tPNS treatment in PC-3 cells. The aforementioned results indicated that tPNS inhibited PC-3 cell migration by suppressing MMP-2 and VCAM-1 expression. The phosphorylation level of the p38 MAPK pathway was dramatically increased at 0.5, 1, 3, and 6 h after tPNS treatment ( 400 mg/L ). However, phosphorylation of the ERK pathway was unaffected. Conclusion: tPNS can inhibit the proliferation and migration of PC-3 cells. The underlying mechanism may be related to the expression of PCNA, VCAM-1, and MMP-2 and activation of the p38 MAPK pathway.