Density functional methods (B3LYP, B3PW91, B3P86, and MPWB95) with 6–31G** basis sets and complete basis methods are employed to investigate the bond dissociation energies (BDEs) of the O–NO2 bond for seven O-nitroalcohol compounds in acetonitrile solution. B3LYP/6–31+G**, (RO)B3LYP/6–311++G(2df,2p), and B3LYP/6–311G(d,p) methods are also used. By comparing the calculated results with the experimental values, B3LYP/6–31+G** is the most accurate method to compute the reliable BDEs for the studied compounds. The substituent effects on the O–NO2 BDEs are analyzed. It is found that electron-withdrawing groups increase the BDE of the parent compound, whereas electron-donating groups decrease the BDE of the parent compound. Further, the natural bond orbital analysis shows that there exist good linear correlations between E(2) and Hammett constants, the BDE, and the difference of the second-order stabilization energies E(2) of lpO3 → BD*(O1–N1) and lpO3 → BD*(O2–N1).