The electronic properties of double-stranded octametric DNA-DNA and LNA-DNA with a single-base mismatch were compared with those having fully complementary base pairs to quantify the effect of the base mismatch on hybridization energies (HE). A single T-G mismatch in the LNA-DNA gives rise to a significant reduction in HE, which is consistent with a significant lowering of the melting temperature for mismatched LNA-DNA. By contrast, the hybridization strength of the mismatched DNA-DNA depends strongly on local hydrogen-bonding arrangements in the mispaired T-G. The difference in HE is explained in terms of variation in charge distributions around the hydrogen-bonded base pairs.