On-chip nonvolatile photonic switches enabled by phase change materials (PCMs) are promising building blocks for power-efficient programmable photonic integrated circuits. However, large absorption loss in conventional PCMs (such as Ge2Sb2Te5) interacting with weak evanescent waves in silicon waveguides usually leads to high insertion loss and a large device footprint. In this paper, we propose a 2×2 photonic switch based on two-mode interference in a multimode slot waveguide (MSW) with ultralow loss Sb2S3 integrated inside the slot region. The MSW supports two lowest order TE modes, i.e., symmetric TE00 and antisymmetric TE01 modes, and the phase of Sb2S3 could actively tune two-mode interference behavior. Owing to the enhanced electric field in the slot, the interaction strength between modal field and Sb2S3 could be boosted, and a photonic switch containing a ∼9.4 µm-long Sb2S3-MSW hybrid section could effectively alter the light transmission between bar and cross ports upon the phase change of Sb2S3 with a cross talk (CT) less than -13.6 dB and an insertion loss (IL) less than 0.26 dB in the telecommunication C-band. Especially at 1550 nm, the CT in the amorphous (crystalline) Sb2S3 is -36.1 dB (-31.1 dB) with a corresponding IL of 0.073 dB (0.055 dB). The proposed 2×2 photonic switch is compact in size and compatible with on-chip microheaters, which may find promising applications in reconfigurable photonic devices.