diff --git a/newsfragments/4389.fixed.md b/newsfragments/4389.fixed.md
new file mode 100644
index 00000000000..6702efd3a75
--- /dev/null
+++ b/newsfragments/4389.fixed.md
@@ -0,0 +1 @@
+Fix invalid library search path `lib_dir` when cross-compiling.
diff --git a/pyo3-build-config/src/impl_.rs b/pyo3-build-config/src/impl_.rs
index 571f9cb5a0c..ec65259115f 100644
--- a/pyo3-build-config/src/impl_.rs
+++ b/pyo3-build-config/src/impl_.rs
@@ -1438,7 +1438,10 @@ fn cross_compile_from_sysconfigdata(
 ) -> Result<Option<InterpreterConfig>> {
     if let Some(path) = find_sysconfigdata(cross_compile_config)? {
         let data = parse_sysconfigdata(path)?;
-        let config = InterpreterConfig::from_sysconfigdata(&data)?;
+        let mut config = InterpreterConfig::from_sysconfigdata(&data)?;
+        if let Some(cross_lib_dir) = cross_compile_config.lib_dir_string() {
+            config.lib_dir = Some(cross_lib_dir)
+        }
 
         Ok(Some(config))
     } else {