Prosecutor Alessandro Crini also called for a 26-year sentence for Knox's former boyfriend, Raffaele Sollecito.
The retrial at an appeals court in the Italian city of Florence began in September .
Sollecito and Knox were convicted in 2009 of killing Kercher, 21, who was found stabbed in November 2007 in the villa that she and Knox rented in the central Italian university town of Perugia.
Their convictions were overturned in 2011 for "lack of evidence." But Italy's Supreme Court decided last year to retry the case, saying that the jury that acquitted them didn't consider all the evidence and that discrepancies in testimony needed to be answered.
Both Knox, 26, and Sollecito have maintained their innocence.
The retrial began on September 30 without either of them present in court. The presiding judge, Alessandro Nencini, read out the details of the case, including the conviction of Ivory Coast citizen Rudy Guede for his role in Kercher's murder.
In his second day of closing remarks, Crini said both Knox and Sollecito should be convicted and handed a 26-year sentence for homicide, with an additional four years for Knox for slander.
The slander charge relates to Patrick Lumumba, a Congolese bartender whom Knox originally accused of Kercher's murder. Lumumba spent several weeks in jail after Knox accused him, and he won a defamation suit against her.
On Monday, Crini recapped the evidence against Knox and Sollecito and highlighted what he said was suspicious behavior by Knox after Kercher's killing.
Knox has not been in court for the retrial.
She returned to her hometown of Seattle after her acquittal and has been living there since. She says she is afraid to return to Italy, where she spent four years behind bars.
CNN's Hada Messia reported from Rome and Laura Smith-Spark wrote in London.