In Nanjing, G42 first intersects with the southeast portion of G2502 Nanjing Ring Expressway, then follows a partial cloverleaf interchange near Purple Mountain, Qixia District to interchange with northbound G36 Nanjing-Luoyang Expressway. For its entire length south to Yangtze River in Nanjing, G42 concurs with Jiangsu S001 Highway and intersects with G25 Changchun-Shenzhen Expressway near Baixia District. At Huashenmiao Interchange, the expressway interchanges with Jiangsu S55 Nanjing-Xuancheng Expressway/S88 Airport Expressway. Before crossing the Yangtze River, G42 connects to the north-south spur of G4211 Nanjing-Wuhu Expressway and concurs with G2501 again. Through traffic is then carried across the Yangtze River by Third Nanjing Yangtze Bridge, and the G42 splits with G2501 at an interchange to the east of Laoshan National Forest Park, where G42 turns west and concurs with G40 Shanghai-Xi'an Expressway for their remaining lengths in Jiangsu. At the town of Zhouzhuang, Pukou District, the expressway becomes a four-lane expressway and enters Anhui Province at Quanjiao County.