This paper presents a study of closely spaced double tunnels in Taizhou, China. One is Xiabei Mountain No. 2 four-line super-span high-speed railway tunnel (HRT), and the other is Xiabei Mountain double-line large-span subway tunnel (ST). The excavation spans of HRT and ST are 26.3 and 14 m, respectively. The two tunnels are located at different levels, and their separating distance is 17.2 m. Due to the short construction period, the HRT excavation was completed earlier than ST. The structural design of the HRT, taking account of the disturbance by the ST construction, was analyzed by a numerical simulation. It was found that the “yielding principle” design was more feasible than the “resistance principle” design when considering the safety and durability of the HRT secondary lining. The mechanical responses of the HRT during ST construction were comprehensively monitored and analyzed, including the vault settlement, horizontal convergence, surrounding rock pressure, and the internal stress in shotcrete and steel arch. Results show that the longitudinal influence range of the ST construction on the HRT was approximately 0.6–1.1 times the ST outer diameter; the disturbance was mainly generated in the ST upper bench excavation; and the final axial force of the HRT shotcrete was approximately 9–16 times that of the steel arch, which indicated that the shotcrete was the main bearing structure. The safety status of the HRT was assessed based on the monitoring data, and the minimum safety factors of the HRT shotcrete and steel arch were 1.61 and 1.89, respectively. Parametric studies were performed to show how the lining stress of HRT was affected by the relative angle, pillar width, ST excavation method and excavation footage. Finally, the design and construction optimization were proposed according to the monitoring data and parameter analysis results. This study might provide practical reference for similar projects.