We report here that the hyper-Rayleigh scattering (HRS) technique which has emerged over the past decade as a powerful method to determine the microscopic non-linear optical (NLO) properties of species in solution, can be used to achieve the ultra-sensitive detection of single base-pair mismatch in oligonucleotide strands without any modification of DNA. A very distinct HRS intensity change has been observed after hybridization even at the concentration of 15 nanomolar probe ss-DNA. The HRS intensity enhanced by a factor of 20 after hybridization. The HRS intensity did not change when we added the target DNA with one base-pair mismatch with respect to probe DNA. Size dependent optical absorption and hyper Rayleigh scattering properties have been measured. The mechanism of size and distant dependence HRS intensity changed has been discussed.