Tan Sri Dr. Ali bin Hamsa was a tutor in University of Malaya prior to starting his career in the Administrative and Diplomatic Service (PTD) as an Assistant Director at the Ministry of Trade and Industry on 5 January 1981. 

In 1986, he was appointed as the Senior Project Manager, Economy and Public Policy Management Centre (PUTERA) at the National Institute of Public Administration (INTAN), where he co-authored two books, namely Dasar-Dasar Utama Kerajaan (1988) and Malaysia Kita (1990). He had a short stint at the Ministry of Transport in 1992. 

Upon obtaining his Ph.D in 1997, he began serving at the Economic Planning Unit (EPU), Prime Ministers Department. He held the position of Director of Department. He held the positions of Director of Distribution and Deputy Director-General of the National Transformation and Advancement Programme. On 22 April 2009, Tan Sri Dato' Sri Dr. Ali bin Hamsa was appointed as the first Director-General of the Public Private Partnership Unit (UKAS), Prime Ministers Department. 

He served as the 13th Chief Secretary to the Government of Malaysia from 24 June 2012 until 28 August 2018. As of to date, he holds the Directorships in YB Ventures Berhad, G Capital Berhad, and KPJ Healthcare Berhad.

1. KPJ Healthcare Berhad (Public Listed)
2. YB Ventures Berhad (Public Listed)
3. G Capital Berhad (Formerly known as Gunung Capital Berhad) (Public Listed)
4. Kulim (Malaysia) Berhad
5. NCB Holdings Berhad

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