Holy Cross Church is a Roman Catholic church located at 329 West 42nd Street between Eighth and Ninth Avenues in the Hell's Kitchen neighborhood of Manhattan, New York City, near Times Square and across the street from the Port Authority Bus Terminal.
The Holy Cross Parish was established in 1852 and a chapel erected, which the congregation quickly outgrew. In 1854, a new building was constructed and dedicated, but lightning struck this second structure in 1867, and the ensuing fire severely damaged it. The current church was constructed to a design by Henry Engelbert on the site of the damaged building and completed in 1870. It is notable as the oldest building on 42nd Street. The Holy Cross School, located behind the church at 332 West 43rd Street, was built in 1887 to a design by Lawrence J. O'Connor.
Since 1900, Holy Cross Church has worked with politicians, police and community groups to combat poverty, crime and drugs in the neighborhood. The parish is especially associated with the popular ministry of the Reverend Francis P. Duffy.