PIA operated two flights in a week (Monday and Thursday) between the commercial capitals of Pakistan and India, Karachi and Mumbai.
However, the PIA's Lahore-Delhi flight operation will continue as traffic volume on this route is satisfactory, the PIA official told PTI.
The suspension of Karachi-Mumbai route may add traffic to Lahore-Delhi route, he said.
"There will be no PIA flight between Karachi to Mumbai and Mumbai to Karachi from April 8. The PIA has stopped booking for flights on this route," the official said.
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"Since we have been bearing financial loss on this route for the last six months or so we have arrived at a decision to suspend this route," the official said, adding that unless a special subsidy is not given by the government on this route it may not be restored in the near future.
The move comes amid a strain in Indo-Pak ties following the beheading of two Indian soldiers by the Pakistan military in Jammu and Kashmir.
The PIA administration, however, dismissed media reports that the Karachi-Mumbai operation is being suspended due to tense relations between India and Pakistan.
The proposal to suspend the Karachi-Mumbai flight may have been made for commercial purposes, but deteriorating ties indirectly have affected traffic on the route.
PIA was a profit making entity and earned more than Rs 2 billion in 2004 but after that it went into deficit and could not recover.
Since 2013, when the current Nawaz Sharif government took over, the carrier has suffered more than Rs 100 billion in losses, according to officials.