New X-substituted 1,3,2-oxazaphosphorinanes, where X = NHC6H5 (1), NHC6H4S(O)2NH2-4 (2), NHC6 H4OCH3-4 (3), NHC6H4NO2-4 (4), OC6H4CH3-4 (5), NHC(O)C6H4NO2-4 (6), plus one X-substituted 1,3,2-diazaphosphorinane, where X = NHC6H4S(O)2NH2-4 (7), were synthesized and characterized by NMR, IR spectroscopy, and elemental analysis. The antitumor activities of these compounds, cyclophosphamide (CP), sulfanilamide (SA), and two X-substituted 5,5-dimethyl-1,3,2-diazaphosphorinanes, where X = NHC6H5 (8) OC6H4CH3-4 (9), were evaluated by cell culture on K562, MDA-MB-231, and HepG2 cell lines using MTT cell proliferation assay. The IC50 values for CP and compounds 1–9 were in the range of 0.06 lM (for inhibition of HepG2 cells by compound 3) to 3.17 lM (for inhibition of HepG2 cells by compound 8). It was found that compounds 2 and 7 containing sulfonamide substituent and also SA itself are the best candidates for antitumor activity very close to CP.