The lack of in-depth understanding on the low-temperature fatigue cracking performance has limited the extensive application of the Q345qD bridge steel in cold and severely cold regions. This study investigates the resistance to the fatigue crack initiation of the Q345qD steel through a series of strain-controlled fatigue tests of smooth coupons at room and low temperatures. Experimental results present the cyclic stress-strain relationship, non-Masing properties and Coffin-Manson-type fatigue crack initiation resistance. Thereafter, this study analyzes the effect of low temperatures on the stain-controlled fatigue life of the studied Q345qD steel using the different energy approaches. Results indicate that the low temperatures within -60 °C increase the resistance to the fatigue crack initiation and the cyclic strain-hardening coefficients. A comparison with other structural steels demonstrates the excellent fatigue performance of the Q345qD steel at room and low temperatures. Since the corresponding stress amplitudes of the Q345qD steel under each cyclic strain range exhibit some strain-range-dependent cyclic softening/hardening behavior, the plastic strain energy density and the concept of fatigue toughness are more suitable and effective to predict the fatigue life of the Q345qD steel at room and low temperatures. Finally, a simple and accurate method for calculating the plastic strain energy density has been proposed.