Aiming at improving the performance of 22 mm thick X80M hot rolled steel strip DWTT performance, simulated tests and industrial trials were carried out on a 550 mm test mill and a 2250 mm hot tandem mill. The effects of different starting temperature and the end temperature of finish rolling, cooling rate, coiling temperature on the microstructure and DWTT properties of the test steel were studied. The effects of austenite grain size on DWTT properties were studied by comparing the rough rolling reduction rate and the accumulative deformation rate in the non-recrystallized zone. The results show that uniform and fine original austenite grains can obtain uniform, and fine acicular ferrite lath bundles. The microstructure of acicular ferrite, granular bainite and a large number of fine M/A islands dispersed on ferrite matrix with high density dislocations has better DWTT performance. Meanwhile, the average effective grain size of X80M pipeline steel can be refined to obtain more grain boundary area per unit volume. Large angle grain boundary is beneficial to prevent crack propagation. Improving grain size of X80M pipeline steel strip is an effective measure to improve fracture toughness. Under this chemical composition, the final pass reduction ratio in roughing mill of X80M pipeline steel is ≥26%, the thickness of intermediate slab is 68 mm,the starting temperature of finish rolling is 900 °C, the end temperature of finish rolling is 810 °C, the cooling rate is 25 °C/s, the coiling temperature is below 400 °C, and DWTT toughness fracture ratio can reach more than 85%, which can meet the application requirements of pipeline steel for the extreme conditions of −15 °C in the west-east gas pipeline.