The objective was to investigate the effects of running shoes with midsole hollow structure span and height on the biomechanics of the lower limbs during running. We collected 21 adults with running habits who wore two pairs of running shoes with different midsole hollow structures and ran at a speed of 3.3[Formula: see text]m/s on a force-measuring treadmill. The lower limb kinematics, ground reaction force (GRF) and lower limb muscle activation characteristics were simultaneously captured by a motion capture system, a 3D force treadmill, and a surface electromyography (sEMG) system. Paired t-tests were performed on data for the two shoe conditions that fit the normal distribution assumptions; otherwise, Wilcoxon signed-rank tests were used. The statistical parameter mapping (SPM) technology was used for the analysis of 1D parameters of kinematic, dynamic, and sEMG activation characteristics. The result showed that the time to the peak impact force at touchdown of Hollow shoe2 was significantly increased ([Formula: see text]), the maximum loading rate ([Formula: see text]) and average loading rate ([Formula: see text]) were significantly reduced, braking time ([Formula: see text]), push time ([Formula: see text]), contact time ([Formula: see text]) of Hollow shoe2 were significantly increased compared with Hollow shoe1. Hollow shoe2 push phase of the tibialis anterior muscle activation characteristics was significantly lower (SPM, [Formula: see text]) than Hollow shoe1. Our conclusion is that running shoes offer the solution as they have the advantage of the complex structure of the hollow midsole.