Shell-side two-phase pressure drops under cross-flow condition play an important role in the operation of heat exchangers. However, no well-verified general correlation for predicting two-phase friction multipliers in horizontal tube bundles is available in the open literatures. In the present paper, based on a combination of Kanizawa and Ribastki flow regime criteria with the modified Mao and Hibiki flow regime criteria, the flow patterns of two-phase vertically upward flow across horizontal tube bundles in the open literatures were identified. The results show that flow patterns have a significant effect on two-phase friction multipliers. For the bubbly flow, finely dispersed bubbly flow, and annular flow, the mass velocity effect on two-phase friction multipliers can be neglected. However, the two-phase friction multipliers of cap bubbly flow and churn flow decrease with an increasing mass velocity. Then, a general dimensionless correlation in terms of the Martinelli parameter and the two-phase Froude number were developed, which is able to accurately predicting gas–liquid two-phase flow resistances of churn flow in staggered horizontal tube bundle under cross-flow condition. New correlations for predicting two-phase friction multipliers of bubbly flow, finely dispersed bubbly flow and annular flow both in staggered and in-line horizontal tube bundles were also developed and can give excellent representations for the existing data in the open literatures.