In this work, tumor acidity and CD44 dual targeting hyaluronic acid-coated gold nanorods (AuNRs) are investigated for combined chemo- and photothermal cancer therapy. Low molecular weight hyaluronic acid (LMWHA) is conjugated with pH-sensitive groups for pH-induced aggregation and lipoic acid for coating of AuNRs. By changing pH-sensitive groups with different pKa values, pH-sensitivity of modified LMWHA can be tuned. After coating modified LMWHA onto AuNRs, biocompatibility of the AuNRs is significantly improved. These LMWHA-coated AuNRs can gradually aggregate under slightly acidic conditions, making them favorable for accumulation at acidic tumor sites. Surface LMWHA allows the nanocomposites to be selectively uptaken by CD44-expressing cancer cells, and AuNRs endows the nanocomposites with excellent photothermal ability. Loading of doxorubicin, a chemical drug, provides the LMWHA-coated AuNRs synergistic cancer cell-killing (in vitro) and tumor growth inhibiting (in vivo) ability. Taken together, these results demonstrate that this multifunctional nanosystem with pH-induced aggregation and CD44 targeting has potential for combined chemo- and photothermal cancer therapy.