diff --git a/llvm/lib/Target/AMDGPU/SIFoldOperands.cpp b/llvm/lib/Target/AMDGPU/SIFoldOperands.cpp
index cc15dd7cb495c..46bd5d8044c45 100644
--- a/llvm/lib/Target/AMDGPU/SIFoldOperands.cpp
+++ b/llvm/lib/Target/AMDGPU/SIFoldOperands.cpp
@@ -1453,7 +1453,7 @@ bool SIFoldOperandsImpl::tryFoldZeroHighBits(MachineInstr &MI) const {
     return false;
 
   std::optional<int64_t> Src0Imm = getImmOrMaterializedImm(MI.getOperand(1));
-  if (!Src0Imm || *Src0Imm != 0xffff)
+  if (!Src0Imm || *Src0Imm != 0xffff || !MI.getOperand(2).isReg())
     return false;
 
   Register Src1 = MI.getOperand(2).getReg();
diff --git a/llvm/test/CodeGen/AMDGPU/fold-zero-high-bits-skips-non-reg.mir b/llvm/test/CodeGen/AMDGPU/fold-zero-high-bits-skips-non-reg.mir
new file mode 100644
index 0000000000000..b1aa88969c5bb
--- /dev/null
+++ b/llvm/test/CodeGen/AMDGPU/fold-zero-high-bits-skips-non-reg.mir
@@ -0,0 +1,17 @@
+# NOTE: Assertions have been autogenerated by utils/update_mir_test_checks.py UTC_ARGS: --version 5
+# RUN: llc -mtriple=amdgcn -mcpu=gfx1101 -run-pass si-fold-operands %s -o - | FileCheck %s
+---
+name: test_tryFoldZeroHighBits_skips_nonreg
+tracksRegLiveness: true
+body: |
+  bb.0:
+    ; CHECK-LABEL: name: test_tryFoldZeroHighBits_skips_nonreg
+    ; CHECK: [[V_MOV_B32_e32_:%[0-9]+]]:vgpr_32 = V_MOV_B32_e32 0, implicit $exec
+    ; CHECK-NEXT: [[REG_SEQUENCE:%[0-9]+]]:vreg_64 = REG_SEQUENCE [[V_MOV_B32_e32_]], %subreg.sub0, [[V_MOV_B32_e32_]], %subreg.sub1
+    ; CHECK-NEXT: [[V_AND_B32_e64_:%[0-9]+]]:vgpr_32 = V_AND_B32_e64 65535, 0, implicit $exec
+    ; CHECK-NEXT: S_NOP 0, implicit [[V_AND_B32_e64_]]
+  %0:vgpr_32 = V_MOV_B32_e32 0, implicit $exec
+  %1:vreg_64 = REG_SEQUENCE %0, %subreg.sub0, %0, %subreg.sub1
+  %2:vgpr_32 = V_AND_B32_e64 65535, %1.sub0, implicit $exec
+  S_NOP 0, implicit %2
+...