Lien's first television appearance was in a bubble gum commercial playing twins. Her first appearance on a television series was as a music academy student in a 1990 episode of Brewster Place, starring Oprah Winfrey. The same year she provided her voice for the dubbed English language version of Baby Blood, a French horror film. Lien moved to New York in 1991 after she was cast as Hannah Moore on the series Another World. She attended and graduated from the Professional Children's School while working on this series.

In a 1992 interview, Lien said: "A couple of years ago, I was trying to get an audition for a baseball movie, so I said that I could play baseball. We’d always played a lot while I was growing up, like in the backyard. But when I showed up at the audition, I was faced with these Goliath-like, testosterone women who could really play. I did survive the two days of training and auditions, but I basically pulled every muscle in my body!"

In 1993, Lien was cast as Roanne in Phenom, a sitcom starring Judith Light. She also participated in the recording of Adam Sandler's comedy album They're All Gonna Laugh At You in which she played the part of the Valedictorian on the track "The Buffoon And The Valedictorian", as well as one of the daughters on the track "Oh, mom...".

In 1994, Lien was cast as Kes on Star Trek: Voyager. Her character is an Ocampan, a species in the Star Trek universe that lives for only 8 to 9 years, who joins the starship's crew after it is stranded 70,000 light-years from Earth.

In a 1995 interview, Lien said the following about these conventions:

In a 1996 interview, Lien said about two of her Voyager co-stars: "I was working on a scene in Sickbay the other day with Kate and Bob Picardo, and they - they know what they’re doing. They’re both such good actors. I thought, ‘Oh, God, I’m so lucky to be here!’ I didn’t say anything to them because - I don’t know why I didn’t say anything. It’s probably just not the kind of thing you say to people. I was seeing talent, experience and wisdom in action, inventiveness and creativity happening in front of me. It’s a good job I have."

After Voyager, Lien appeared in the movie American History X as older sister Davina Vinyard alongside Edward Norton's character Derek Vinyard. In 1998, she appeared in SLC Punk! playing Sandy, the wild girlfriend of Matthew Lillard's character Stevo. She also voiced Agent "L" for the first three seasons of Men in Black: The Animated Series (1997-1999) and the first 7 episodes of the 2000 season.

In a 2000 interview, Lien revealed that she liked every kind of music, and that she played the trombone, which she started in high school. She said she supported charities helping people with AIDS and had worked with Camp 40, of which she said: "I want to be doing what I can for people who need it."

Lien is married to Writer and filmmaker Phil Hwang; their son, Jonah, was born on September 5, 2002. Upon the birth of her son, Lien retired from acting and voice-over work but was credited as executive Producer on her husband's 2008 film Geek Mythology. In August 2010, Lien said she intended to work as a nutritionist after completing her studies.

Lien has had run-ins with the law from 2012 to 2018 which resulted in her being charged with a number of offences including domestic violence, indecent exposure and vehicle related offences, and led to her undergoing mental health treatment.