He hailed from Rencheng 任城 (modern Qufu 曲阜, Shandong) and was known for his love for austerity and a simple life. He did not love to make a lot of words but rather used his mind and thought. He Xiu was a retainer of Grand Mentor (taifu 太傅) Chen Fan 陳蕃 and had so the opportunity to give practical advice in government as derived from the Six Confucian Classics (liujing 六經).
Because he was involved in the factional strife between the court officials and the eunuchs, he was banned from any state offices for almost two decades. When the ban on court factions (danggu 黨錮) was lifted, he was appointed court gentleman for consultation (yilang 議郎) and was later promoted to Grand Master of Remonstrance (jianyi dafu 諫議大夫).
The time in exile had helped him to intensify his studies of the Confucian Classics. During that time he wrote his notes on the Gongyang Commentary (Gongyangzhuan 公羊傳) to the Chunqiu 春秋 "Spring and Autumn Annals", the Chunqiu Gongyang jiegu 春秋公羊解詁, which is still preserved today. Together with Master Humu 胡毋生 and Dong Zhongshu 董仲舒, He Xiu is one of the most important early commentors of the Gongyangzhuan.
During the Later Han period, the old-text school on the Confucian Classics gained ground that focused its research and interpretation on the Zuozhuan 左傳 version of the Spring and Autumn Annals (also called Zuoshi chunqiu 左氏春秋), while less and less scholars were interested in the Gongyang commentary. Those still writing about the Gongyangzhuan had a tendency to the apocryphal interpretation of the Classics.
He Xiu was one of the few scholars defending the study of the Gongyangzhuan in a non-speculative way and thus fought both against the old-text school preferring the Zuozhuan and the apocryphal tradition. His commentary was geared to the guidelines (tiaoli 條例) established by Humu Sheng but also included thoughts of Dong Zhongshu's explanation of the world in his famous Chunqiu fanlu 春秋繁露. He quotes also from sources like the Yanshi chunqiu (1) 嚴氏春秋 and Yanshi chunqiu (2) 顏氏春秋, the first of which is lost, as well as from the works of Li Yu 李育 and Yang Bi 羊弼.
He Xiu thus became an important collector of the Han-period interpretation of the Gongyang commentary and made it one important work extending the teachings of Confucius not only in the sphere of human interrelations, but also to the sphere of government. A ruler reading and understanding He Xiu's commentary would, he hoped, be able to save the declining Han dynasty.
He Xiu indirectly criticized the power struggles between officials and eunuchs at the court of the emperors Huan 漢桓帝 (r. 146－167) and Ling 漢靈帝 (r. 167-189) and the intrusion of the eunuchs into government affairs. Instead, the rulers would have to promote competent and wise ministers, to lower taxes and to contain the growing power of the large land owners and their exploitation of the peasant population.
The other books of He Xiu, Gongyang moshou 公羊墨守, Zuoshi gaohuang 左氏膏肓 and Guliang feiji 榖梁廢疾 are only preserved in fragments collected by the Qing period 清 (1644-1911) scholar Wang Mo 王謨 in his Han-Wei yishu chao 漢魏遺書鈔. He Xiu had also commented the Classics Xiaojing 孝經 and Lunyu 論語.