The Taiping Rebellion in the mid-19th century was the first major instance of anti-Manchu sentiment threatening the stability of the dynasty. Hong Xiuquan, a failed civil service candidate, led the Taiping Rebellion, amid widespread social unrest and worsening famine. In 1851 Hong Xiuquan and others launched an uprising in Guizhou province, established the Taiping Heavenly Kingdom with Hong himself as king, claiming he often had visions of God and that he was the brother of Jesus Christ. Slavery, concubinage, arranged marriage, opium smoking, footbinding, judicial torture, and the worship of idols were all banned. However, success and subsequent authority and power led to internal feuds, defections and corruption. In addition, British and French troops, equipped with modern weapons, had come to the assistance of the Qing imperial army. It was not until 1864 that Qing armies under Zeng Guofan succeeded in crushing the revolt. The rebellion not only posed the most serious threat towards Qing rulers; it was also "bloodiest civil war of all time." Between 20 and 30 million people died during its fourteen-year course from 1850 to 1864. After the outbreak of this rebellion, there were also revolts by the Muslims and Miao people of China against the Qing dynasty, most notably in the Dungan Revolt (1862–77) in the northwest and the Panthay Rebellion (1856–1873) in Yunnan.

What marked the first occurence of anti-Manchu feeling?