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The Church of the Most Precious Blood is a Roman Catholic parish located in New York City. The parish is under the authority of the Archdiocese of New York, and is the National Shrine Church of San Gennaro. Located on 109 Mulberry Street in New York, the Church of the Most Precious Blood is part of New York's Little Italy neighborhood.

During the Feast of San Gennaro, which is held yearly in September, a celebratory Mass is held at the church on the last Saturday of September. Following this, the statue of San Gennaro is taken from its home within the church on a procession through the streets of Little Italy. The building of this church was begun by the Scalabrini Fathers in the late 19th Century. The Scalabrini Order built the foundation but ran out of funding. The Franciscans then took over the parish and completed the church building.

This church was built as an Italian National Parish, geographically located within the territory of Transfiguration Parish. This Church also houses the National Shrine to San Gennaro. While this parish no longer offers a weekly mass in Italian, it now has a large and growing Vietnamese congregation and offers weekly mass and Rosary recitation in the Vietnamese language.