The possibility of the utilization of chemiluminescence post-column luminol oxidation (CL) in a HPLC system for silyl peroxides analysis has been investigated. The conditions of HPLC separation for 12 silyl peroxides, representing bissilyl and alkyl-silyl peroxides, as well as their potential impurities, were established. Optimal chemiluminescent post-column reaction conditions were found using central composite design (CCD) and response surface methodology (RSM). The interaction effects of four of the most important operating variables – the concentrations of luminol, hemin, sodium hydroxide and the post-column solution flow rate – on the light intensity were evaluated. The optimized conditions for analysis were the same for bissilyl and alkyl-silyl peroxides for the base concentration (0.03M), the luminol concentration (0.4gL−1) and the hemin concentration (0.3gL−1). The only differences occurred in a reagent flow rate (for bissilyl peroxide −0.3mLmin−1 and for alkyl-silyl peroxides −0.9mLmin−1).Under optimal conditions, the detection limits were in the 0.07–0.16nM range for bissilyl, and 0.53–1.01 for alkyl-silyl peroxides. The calibration curves were linear in the 0.25–3nM range for bissilyl and the 2.5–25 range for alkyl-silyl peroxides. Intra-day and inter-day precision was lower than 5.5% for each tested concentration level. A mechanism of luminol oxidation by silyl peroxides involving a hydrolysis step with the formation of hydrogen peroxide or hydroperoxide was proposed.