The invention relates to the technical field of antibiotic products, and particularly provides a novel tylosin premix and a preparation process and application thereof. The novel tylosin premix is prepared from an anti-caking agent, an adsorbent, an adhesive, a diluent and other ingredients in a certain ratio. The preparation process comprises the following steps: (1) preparing materials; (2) smashing and sieving; (3) mixing uniformly; (4) pulping; and (5) drying and granulating. The novel tylosin premix is mixed with pig feed for use, accounts for 0.2wt% of the pig feed and is fed for 7 dayscontinuously. The novel tylosin premix has the advantages of high drug utilization, good animal adaptability, effective diseased pig treatment, simple manufacture process, convenient production and utilization and small side effect, and particularly has a good curative effect on cough and asthma and clostridiosis welchii of diseased pigs.