In this paper, polyhexamethylene biguanidine hydrochloride (PHMB) oligomers were prepared by polycondensation of hexamethylenediamine, hydrochloric acid and 1,6-hexamethylenebis(dicyanamide); the organosilicon derivatives of PHMB oligomers (PHMB-Si) were prepared in solution through the reaction of PHMB and 3-Glycidoxypropyltrimethoxysilane (GLYMO). The analyses of FT-IR, 1 H and 13 C-NMR, elemental analysis, and TGA showed that the PHMB-Si was synthesized successfully. The relationship between antibiotic activity and viscosity-average molecular weight of PHMB; the relationship between antibiotic activity and the content of organosilicon in PHMB-Si were investigated. The experimental results revealed that the antibacterial activity of PHMB yielded the maximum at the viscosity-average molecular weight of 9000. The higher ratio of GLMYO in PHMB-Si, the higher antibiotic activity of PHMB-Si was. The minimal bactericidal concentration (MBC) of PHMB was 10 ppm, and the MBC of PHMB-Si was 5 ppm. The results showed there was an obvious synergy of PHMB-Si in bacteriostatic activity than PHMB.