Han played a cynical Veterinarian in Padam Padam, written by famous drama Writer Noh Hee-kyung, which aired on newly launched cable channel jTBC. She then starred in Rooftop Prince, about a Joseon-era Prince who time-travels to the 21st century where he meets his dead beloved's doppelgänger. The popularity of Rooftop Prince garnered Han several awards, and increased her international profile, notably in Japan.

Han Ji-min started her career in show Business while still a high school student. She did various commercial films (CF) and music videos before gaining wider attention in 2003, when she appeared in hit Korean television dramas All In and Dae Jang Geum. Han said she hadn't dreamed of becoming a serious Actress, but changed her mind after starring in All In, where she played the teenage counterpart of the drama's main character, played by popular Actress Song Hye-kyo.

Han achieved breakthrough with her performance in the critically acclaimed mania drama Resurrection in 2005. She then challenged herself by playing a cute yet ambitious tomboy who dreams of becoming a pilot in her first movie Blue Swallow.

A Social Welfare major from Seoul Women's University, Han is widely known for actively participating in volunteer work and fund drives, mostly through the relief organization Join Together Society. In 2009, she published her own book titled We’re Already Friends: Han Ji-min's Philippines Donation Book, which includes stories and drawings of her time spent in a deep mountain village in the Philippines helping at a village school. She then donated all the royalties to help in funding the education of children in North Korea and developing countries in Asia.

In 2012, she was designated as goodwill ambassador of the United Nations Environment Programme.

In October 2013, Han left her talent agency S.M. Entertainment's SM C&C and joined Lee Byung-hun's BH Entertainment.

In 2014, she starred in the opposites-attract romantic comedy film The Plan Man, about a methodical, mysophobic librarian who falls for a spontaneous, adventurous musician. Following that, she played the dowager Queen Jeongsun in period film The Fatal Encounter, who is the fierce political rival of her step-grandson King Jeongjo. Han next reunited with The Fatal Encounter co-star Hyun Bin in the 2015 suspense series Hyde, Jekyll, Me, in the role of a circus master who falls for a theme park owner with split personality disorder.

In 2016, Han starred in action thriller The Age of Shadows, based on the 1920s about anti-Japanese independence workers' plots and betrayals.

In 2017, Han was cast in the film Miss Baek, playing the titular protagonist; an ex-convict who is emotionally closed up due to the social stigma. Han also joined the cast of comedy-drama Keys to the Heart. In November, she was cast in romantic short film titled Two Rays of Light alongside Park Hyung-sik.

In 2018, Han is set to return to the small screen with romance fantasy drama Knowing Wife.