Regina DeFrancisco was born on October 17, 2002. She grew up in Chicago, Illinois. Regina had a sister named Margaret DeFrancisco. The two sisters were known for their close bond during their early years.

Their childhood was spent in the Pilsen neighborhood of Chicago. This area had a diverse community, and they attended local schools. Regina was described as a typical teenage girl at school. She had friends and took part in various activities common for teenagers.

As they grew older, Regina and Margaret formed a friendship with a group of peers. This group began to influence their actions and decisions. Their lives took a different direction as they became involved in a serious incident.

On June 6, 2000, Regina DeFrancisco contacted her boyfriend, 22-year-old Oscar Velazquez, and asked him to come over to her home. Along with Regina, her sister Margaret and their friend Veronica Garcia were also present. Veronica had previously given Margaret a gun that belonged to her boyfriend, believing that it would be used for robbery. During the visit, Margaret shot Oscar in the back of the head, killing him instantly.

After the murder, Regina and Margaret stole $600 from Oscar. They then placed his body into his Camaro Z28 and drove it to a vacant lot. There, Regina used nail polish remover to set his body on fire. An anonymous person reported the blaze to 911, leading to the discovery of Oscar's body. The sisters attempted to sell the Camaro but were unsuccessful, so they abandoned the car and set it on fire as well. When police began investigating, Regina and Margaret became suspects, but their accounts did not match, and they fled before arrest.

Regina was captured on October 18, 2002, in Dallas, Texas, after a traffic stop and a high-speed chase. She, like her sister, faced charges for murder and fleeing prosecution. In July 2004, their trial began. Both sisters claimed self-defense in their testimonies. Veronica Garcia, who took a plea deal, testified against the sisters.

The jury found Regina guilty of murder during an armed robbery after six-and-a-half hours of deliberation. Margaret's jury could not reach a decision, leading to her release on bail for a retrial. In November 2004, she was retried and subsequently convicted of first-degree murder.

On September 9, 2004, Regina was sentenced to 35 years in prison. Margaret received a 46-year sentence on December 14, 2004. Both sisters remain incarcerated at Logan Correctional Center. Their friend Veronica served five years for her part in the crime.