Selectins dominate the formation of the metastasis niche and are considered important targets for exploring antimetastatic drugs. In this study, we evaluated the effect of the marine drugglycol alginate sodium sulfate (PSS) and a series of PSS derivatives on P-, L- or E-selectin-mediated binding with tumor cells. We found that PSS effectively prevented the binding of P- or L-selectin with tumor cells. Moreover, the structure-activity relationship study indicated that the activity of PSS is related to the sulfate group at the C-2/C-3 position, the glycol substituent at the C-6 position, the ratio ofguluronic acidto mannuronic acid, and themolecular weight. Additionally, PSS derivatives significantly suppressed lung metastasisin vivo.Our results demonstrated that PSS and its derivatives are potential antimetastatic drugs candidates.Selectins dominate the formation of the metastasis niche and are considered important targets for exploring antimetastatic drugs. In this study, we evaluated the effect of the marine drug glycol alginate sodium sulfate (PSS) and a series of PSS derivatives on P-, L- or E-selectin-mediated binding with tumor cells. We found that PSS effectively prevented the binding of P- or L-selectin with tumor cells. Moreover, the structure-activity relationship study indicated that the activity of PSS is related to the sulfate group at the C-2/C-3 position, the glycol substituent at the C-6 position, the ratio ofguluronic acidto mannuronic acid, and themolecular weight. Additionally, PSS derivatives significantly suppressed lung metastasisin vivo.Our results demonstrated that PSS and its derivatives are potential antimetastatic drugs candidates.