A number of Miss McKee’s friends walked to Junior McDaid House in Chamberlain Street, where they used a pot of red paint to place handprints on the side of the office walls.
A group of some six men, understood to be members of republican group Saoradh, who are associated with the New IRA, stood outside the building during the intense protest.
One of those was Thomas Ashe Mellon (pictured above sporting black beard) who was jailed in 2015 over an attempt to smuggle a note to dissident prisoners in Maghaberry jail.
Police officers were also present and later asked for the names of those involved in the incident.
The dissident republican New IRA is being blamed for shooting the young journalist in the head.
The gunman was aiming at police during disturbances in the Creggan when he hit the 29-year-old on Thursday.
Her killing has been widely condemned across the political spectrum.
Lyra’s friend Sinead Quinn, who took part on Monday’s protest, said: “We have used red paint because they have blood on their hands for what has happened.
“They have encouraged it, they have moulded these young people into what they are and they are standing behind them handing them guns.
“They need to take responsibility today for what has happened.
“They have shirked it so far by saying it was an accidental shooting. You don’t shoot accidentally.”
She added: “When you put a gun into someone’s hand and they shoot it, that’s murder.
“Lyra deserves more and I am so glad there are so many people here today to see and watch these men looking at us.
“They are not a representation of republican people in this town.
“Those people don’t represent (republicanism). Nobody can advocate shooting into a crowd of people and shooting a 29-year-old woman dead.
“People have been afraid to stand up to people like this, we are not afraid.”
Another friend said: “We have had enough. There is a younger generation coming up in the town and they don’t need guns put in their hands.
“They need jobs, they need a better health service and education.
“They need a life, not a gun put in their hands.”The group of friends have pledged to do more in Lyra’s memory.
“Lyra’s McKee’s name will never be forgotten in this town,” Ms Quinn added.
“We have to do it for her.”
Local resident John Lindsay said: “We are using this as an opportunity to speak out against these people.
“The whole town has told them they are not wanted here.
“They have freedom to speak, they don’t have freedom for violence and they don’t have the right to carry out acts of violence.
“There is mood change here, even hardline republicans are speaking out against them and saying they need to desist.
“My message to them is go away and get off our backs and stop dragging children into the past into a life of misery.”
The protest comes as up to 200 members and supporters of Saoradh took part in an Easter Monday commemoration march in west Belfast.
A similar march that was to be held in Derry today, Easter Monday, was called off following the murder of Lyra.
The group’s national chairman Brian Kenna called for the New IRA to apologise for the murder during a speech he delivered at Milltown Cemetery.
But there has yet been no apology from the New IRA.