We report a strategy for conjugated polymer (CP)-based optical DNA detection with improved selectivity. The high sensitivity of CP-based biosensors arises from light harvesting by the CP and the related amplified fluorescent signal transduction. We demonstrate that the use of magnetic microparticles significantly improves the selectivity of this class of DNA sensors. Compared with previously reported DNA sensors with CP amplification, this novel sensing strategy displays excellent discrimination against non-cognate DNA in the presence of a protein mixture or even human serum. We also demonstrate that the magnetically assisted DNA sensor can conveniently identify even a single-nucleotide mismatch in the target sequence.