Benzopolysulfanes, 4-CH3(OCH2CH2)3NHC(O)-C6H4-1,2-Sx (x = 3–7, and 9) were synthesized with a PEG group attached through an amide bond and examined for water solubility, antitumor activity, and propensity to equilibrate and desulfurate. LCMS and HPLC data show the PEG pentasulfane ring structure predominates, and the tri-, tetra-, hexa-, hepta-, and nonasulfanes were present at very low concentrations. The presence of the PEG group improved water solubility by 50-fold compared to the unsubstituted benzopolysulfanes, C6H4Sx (x = 3, 5, and 7), based on intrinsic solubility measurements. Polysulfur linkages in the PEG compounds decomposed in the presence of ethanethiol and hydroxide ion. The PEG pentathiepin desulfurated rapidly and an S3 transfer reaction was observed in the presence of norbornene, no S2 transfer reaction was observed with 2,3-dimethylbutadiene. The antitumor activities of the PEG-substituted benzopolysulfane mixtures were analyzed against four human tumor cell lines PC3 (prostate), DU145 (prostate), MDA-MB-231 (breast), and Jurkat (T-cell leukemia). The PEG conjugated polysulfanes had IC50 values 1.2–5.8 times lower than the parent “unsubstituted” benzopolysulfanes. Complete cell killing was observed for the PEG polysulfanes with 4 μM for PC3 and DU145 cells, and with 12 μM for MDA-MB-231 cells. The results suggest that solubilization of the polysulfur linkage is a key parameter to the success of these compounds as drug leads.