There were 215 deaths in prison custody in England and Wales last year - the highest number on record.
The Ministry of Justice (MoJ) figures show there were 74 self-inflicted deaths in 2013, including one on the day of a prisoner's arrival into custody.
The number of self-inflicted deaths, defined as suicides and accidental deaths due to a prisoner's own actions, was the highest since 2007.
In 2013 there were also 123 deaths from natural causes, four apparent killings and 14 other deaths which are yet to be classified.
The four killings were the most in a single year since 1998, up from zero in 2012.
The MoJ report said: "Deaths in prison custody increased to 215 in 2013 - the highest number of deaths recorded in prison custody in any calendar year - from 198 in 2012.
"The death rate in 2013 increased to 2.55 deaths per 1,000 prisoners compared with 2.23 in 2012."
Shadow justice secretary Sadiq Khan said: "We should all be alarmed that more people died in prisons last year than ever before. It's worrying that the lessons of previous deaths in custody are being ignored.
"Ministers need urgently to address this problem, find out what the causes are, and do all they can to make sure this tragic statistic is never repeated."
The MoJ figures show an increase in the proportion of self-inflicted deaths in the early stages of custody, with 38% of the fatalities occurring within the first 30 days in prison.
There was one self-inflicted death on the day of arrival and nine within the first two full days in prison service custody.
Michael Spurr, chief executive officer of the National Offender Management Service (NOMS), said: "We are committed to reducing the number of deaths in custody and are carefully investigating the rise in self-inflicted deaths.
"We are applying strenuous efforts to learn from each death and are providing further resources and support to help the safer custody work in prisons.
"Every death is subject to an internal investigation and investigation by the police, the Prisons and Probation Ombudsman, as well as a coroner's inquest, and we consider these carefully to allow us to learn any lessons."
Juliet Lyon, director of the Prison Reform Trust, said: "A marked rise in deaths in custody, together with an increase in disturbances, must prompt Justice Ministers to examine whether severe budget cuts, lower staffing levels and a more punitive approach to people in prison are taking a tragic toll and, if so, to act without delay to restore safety and decency in prisons across England and Wales."