A Biclique cryptanalysis on lightweight block cipher MIBS-80 is presented in this paper. Exploiting two independent related-key difference trails, 4-round Biclique of dimension 4 is constructed and the key space is partitioned. To reduce the computational complexity, the precomputation and meet-in-the-middle technique is applied to sieve out the correct key for 12-round MIBS-80. The data complexity of this cryptanalysis is 2⁵² chosen plaintexts, the computational complexity is about 2^77.13 12-round MIBS-80 encryptions, the storage complexity is about 2^8.17, and the success probability is 1. Compared with the previous known cryptanalysis, the new method has advantages in the storage complexity and success probability.