Arming at the disease characteristics and its influencing factors of the civil structures of operating highway tunnels in the central and western karst area of Guangxi, the structure disease of 111 tunnels on 5 highways in this area are investigated and the lining leakage and lining cracks of 37 tunnels on 3 highways are analyzed in detail from the aspects of surrounding rock grade, surrounding rock lithology, and tunnel burial depth. Through statistics, it is concluded that in the operation of highway tunnels in karst areas, the civil structural diseases mainly locate in lining, portal, maintenance road, and drainage facilities. The main lining diseases are cracks and water leakage, and the relationship between these two diseases and the grade of surrounding rock, lithology, and buried depth of tunnel is as follows: (1) The lining diseases are aggravated with the promotion of surrounding rock grade, in which the lining leakage is mainly concentrated in the sidewall, and the lining cracks are mainly annular cracks. (2) Lining leakage mostly occurs in general limestone and dolomitic limestone, accounting for 46% and 45.9% respectively; Lining cracks are the most serious in dolomitic limestone, accounting for 61%; The maximum density of seepage and crack is in argillaceous rock section, and the minimum density is in limestone section, that is, argillaceous rock section is prone to lining diseases easily. (3) The seepage and crack of lining all appear in 300 m buried depth, and 71.31% of the seepage and 76.52% of the cracks appear in 100 m buried depth section; With the increase of tunnel buried depth, the seepage and crack of lining decrease linearly.