The protesters also denounced verdicts in the trial of former president, his sons and the former police chiefs.
Mubarak and his interior minister Habib el-Adly received life sentences for complicity in the killing of protesters during last year's uprising.
The same court acquitted Mubarak's two sons on separate charges of corruption and Adly's security chiefs were acquitted on charges of killing protesters during the revolution.
Spokesman for the Free Front for Peaceful Change, Essam el-Sherif, said they are supporting such mock trials to ratchet up pressures to re-try all officials of the former regime.
Scores of demonstrators chanting and carrying banners marched from Tahrir toward the nearby cabinet office. They denounced Shafiq and the Mubarak verdicts.
Protesters have been angered by Shafiq's links to ousted president leader Mubarak. Both men are former air force commanders and Mubarak made Shafik prime minister shortly before being overthrown in a popular uprising 16 months ago.
The Brotherhood called on activists to join the demonstration in Tahrir, dubbed the "Friday of Perseverance".
Participants in the one-million-man march call for the retrial of former president Husni Mubarak along with figures of his regime before a revolutionary court presided by independent judges.
Mubarak is now serving a life sentence in Torah Prison after being convicted in the case of killing protesters.
The protesters call also for applying the disenfranchisement law against all figures of the former regime who corrupted political, social and economic life.