diff --git a/pkgs/development/python-modules/setuptools-rust/default.nix b/pkgs/development/python-modules/setuptools-rust/default.nix
index 0ccf20709c5d..a4f2997eac7c 100644
--- a/pkgs/development/python-modules/setuptools-rust/default.nix
+++ b/pkgs/development/python-modules/setuptools-rust/default.nix
@@ -45,12 +45,20 @@ buildPythonPackage rec {
 
   # integrate the setup hook to set up the build environment for cross compilation
   # this hook is automatically propagated to consumers using setuptools-rust as build-system
-  setupHook = replaceVars ./setuptools-rust-hook.sh {
-    pyLibDir = "${python.pythonOnTargetForTarget}/lib/${python.pythonOnTargetForTarget.libPrefix}";
-    cargoBuildTarget = stdenv.targetPlatform.rust.rustcTargetSpec;
-    cargoLinkerVar = stdenv.targetPlatform.rust.cargoEnvVarTarget;
-    targetLinker = "${targetPackages.stdenv.cc}/bin/${targetPackages.stdenv.cc.targetPrefix}cc";
-  };
+  #
+  # Only include the setup hook if python.pythonOnTargetForTarget is not empty.
+  # python.pythonOnTargetForTarget is not always available, for example in
+  # pkgsLLVM.python3.pythonOnTargetForTarget. cross build with pkgsLLVM should not be affected.
+  setupHook =
+    if python.pythonOnTargetForTarget == { } then
+      null
+    else
+      replaceVars ./setuptools-rust-hook.sh {
+        pyLibDir = "${python.pythonOnTargetForTarget}/lib/${python.pythonOnTargetForTarget.libPrefix}";
+        cargoBuildTarget = stdenv.targetPlatform.rust.rustcTargetSpec;
+        cargoLinkerVar = stdenv.targetPlatform.rust.cargoEnvVarTarget;
+        targetLinker = "${targetPackages.stdenv.cc}/bin/${targetPackages.stdenv.cc.targetPrefix}cc";
+      };
 
   passthru.tests = {
     pyo3 = maturin.tests.pyo3.override {