diff --git a/llvm/runtimes/CMakeLists.txt b/llvm/runtimes/CMakeLists.txt
--- a/llvm/runtimes/CMakeLists.txt
+++ b/llvm/runtimes/CMakeLists.txt
@@ -183,6 +183,10 @@
   if(canon_name STREQUAL "LIBC")
     list(APPEND prefixes "LLVM_LIBC")
     list(APPEND prefixes "LIBC_")
+    # The `libc` project may require '-DCUDAToolkit_ROOT' in GPU mode.
+    if(LIBC_GPU_BUILD OR LIBC_GPU_ARCHITECTURES)
+      list(APPEND prefixes "CUDA")
+    endif()
   endif()
 
   string(FIND ${projName} "lib" LIB_IDX)